临床试验/NCT04072952

NCT04072952已完成1 期

A Phase 1/2, Open Label, Dose Escalation, and Cohort Expansion Clinical Trial to Evaluate the Safety, Tolerability, and Pharmacokinetics of ARV-471 Alone and in Combination With Palbociclib (IBRANCE®) in Patients With Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Locally Advanced or Metastatic Breast Cancer, Who Have Received Prior Hormonal Therapy and Chemotherapy in the Locally Advanced/Metastatic Setting

Arvinas Estrogen Receptor, Inc.16 个研究点分布在 1 个国家实际入组 219 人开始时间: 2019年9月22日最近更新: 2026年9月29日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: Arvinas Estrogen Receptor, Inc.
入组人数: 219
试验地点: 16
主要终点: Part A: Number of Participants With Dose Limiting Toxicities (DLTs) During First Cycle of Treatment

研究概览研究设计入排标准研究组 & 干预措施方案终点试验结果研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

This was a Phase 1/2 dose escalation and cohort expansion study and assessed the safety, tolerability and anti-tumor activity of ARV-471 alone and in combination with palbociclib (IBRANCE®) in participants with estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) locally advanced or mBC, who had received prior hormonal therapy and chemotherapy in the locally advanced/metastatic setting.

研究设计

研究类型: 干预性
分配方式: 非随机
干预模型: 序贯
主要目的: 治疗
盲法: 开放（无盲法）

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

Part A, Part B, and Part C:
Participants at least 18 years of age at the time of signing the informed consent.
Participants must have histologically or cytologically confirmed ER+ and HER2- advanced breast cancer for which standard curative therapy is no longer effective or does not exist.
Participants must have measurable or non-measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) (version1.1), with radiologic tumor assessments performed within 28 days of the first dose of therapy.
Participants must be willing to undergo a core biopsy of accessible tumor within 4 weeks prior to the initiation of study treatment and a follow-up biopsy on treatment for ER immunohistochemistry (IHC) testing and pharmacodynamics studies. (Patients without accessible tumor tissue may be eligible after discussion with the Medical Monitor.)
Women must be postmenopausal due to surgical or natural menopause.
Part A:
Participants must have received at least 2 prior endocrine regimens in any setting (neoadjuvant, adjuvant or advanced/metastatic) a CDK4/6 inhibitor and up to 3 prior regimens of cytotoxic chemotherapy in the locally advanced or metastatic setting.
Part B:
Participants must have received at least 1 prior endocrine regimen for a minimum of 6 months in the locally advanced or metastatic setting; if more than 1 prior endocrine regimen has been administered, only one of the regimens must have been administered for a minimum of 6 months in the locally advanced or metastatic setting
Participants must have received a CDK4/6 inhibitor
Participants must have received up to 1 prior regimen of cytotoxic chemotherapy in the locally advanced or metastatic setting
Part C:
Participants must have received at least one prior endocrine regimen.
Participants must have received no more than two prior chemotherapy regimens for advanced disease.

排除标准

Part A, Part B, and Part C:
Participants with known symptomatic brain metastases requiring steroids (above physiologic replacement doses). Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to first dose of study drug, have discontinued high-dose corticosteroid treatment for these metastases for at least 4 weeks and are neurologically stable as judged by the Investigator.
Receipt of prior anti-cancer or other investigational therapy within 14 days prior to the first administration of study drug.
Radiation therapy within 4 weeks of first dose of study drug or prior irradiation to >25% of the bone marrow. Palliative radiation for the alleviation of pain due to bone metastasis will be allowed during the study.

研究组 & 干预措施

Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation)

Experimental

Participants received vepdegestrant 360 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Vepdegestrant (Drug)

Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion)

Experimental

Participants initially received palbociclib 100 mg orally QD starting on C1D1, for 21 days followed by 7 days off and then received vepdegestrant 200 mg QD with food on C1D9, given continuously (28-day cycle). Palbociclib was administered alone from C1D1 to C1D8 prior to starting vepdegestrant on C1D9. Vepdegestrant was administered in tablet form and palbociclib in capsule form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Palbociclib (Drug)

Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation)

Experimental

Participants received vepdegestrant 100 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Vepdegestrant (Drug)

Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion)

Experimental

Participants received vepdegestrant 200 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Vepdegestrant (Drug)

Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation)

Experimental

Participants received vepdegestrant 30 milligrams (mg) orally once daily (QD) with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after the end of treatment (EOT) or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Vepdegestrant (Drug)

Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation)

Experimental

Participants received vepdegestrant 500 mg QD or 250 mg twice daily (BID), orally with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Vepdegestrant (Drug)

Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation)

Experimental

Participants received vepdegestrant 400 mg orally QD with food, given continuously (28-day cycle) in combination with palbociclib 125 mg orally QD for 21 days followed by 7 days off treatment to complete a 28-day cycle. Vepdegestrant was administered in tablet form and palbociclib in capsule form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Vepdegestrant (Drug)

Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation)

Experimental

Participants received vepdegestrant 60 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Vepdegestrant (Drug)

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation)

Experimental

Participants received vepdegestrant 700 mg QD or as BID dose (400 mg in the morning and 300 mg in the evening), orally with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Vepdegestrant (Drug)

Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation)

Experimental

干预措施: Vepdegestrant (Drug)

Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation)

Experimental

Participants received vepdegestrant 120 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Vepdegestrant (Drug)

Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation)

Experimental

Participants received vepdegestrant 180 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Vepdegestrant (Drug)

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion)

Experimental

Participants received vepdegestrant 500 mg orally QD with food in continuous daily dosing (on 28-day cycles). Vepdegestrant was administered in tablet form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Vepdegestrant (Drug)

Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion)

Experimental

Participants received vepdegestrant 200 mg orally QD with food, given continuously (28-day cycle) in combination with palbociclib 125 mg orally QD for 21 days followed by 7 days off treatment to complete a 28-day cycle. Vepdegestrant was administered in tablet form and palbociclib in capsule form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Palbociclib (Drug)

Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion)

Experimental

Participants received vepdegestrant 500 mg orally QD with food, given continuously (28-day cycle) in combination with palbociclib 125 mg orally QD for 21 days followed by 7 days off treatment to complete a 28-day cycle. Vepdegestrant was administered in tablet form and palbociclib in capsule form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed for survival every 3 months after EOT or Follow-up visit (whichever occurred later) until death, lost to follow-up, or withdrawal of consent.

干预措施: Palbociclib (Drug)

Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation)

Experimental

Participants initially received vepdegestrant 180 mg tablets orally QD with food then upon availability of the 100-mg tablets was rounded up to 200 mg QD, given continuously (28-day cycle) in combination with palbociclib 125 mg orally QD for 21 days followed by 7 days off treatment to complete a 28-day cycle. Vepdegestrant was administered in tablet form and palbociclib in capsule form. Treatment was continued at the investigator's discretion until disease progression, unacceptable toxicity, or withdrawal of consent occurred. Participants were followed up for survival after at least 3 months after the EOT or Follow-up visit (whichever occurred later).

干预措施: Palbociclib (Drug)

Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation)

Experimental

干预措施: Vepdegestrant (Drug)

Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion)

Experimental

干预措施: Vepdegestrant (Drug)

Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion)

Experimental

干预措施: Vepdegestrant (Drug)

Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation)

Experimental

干预措施: Palbociclib (Drug)

Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion)

Experimental

干预措施: Vepdegestrant (Drug)

方案终点

主要结局

Part A: Number of Participants With Dose Limiting Toxicities (DLTs) During First Cycle of Treatment

时间窗: Baseline (Day 1) up to C1D28

DLT was defined as any adverse event (AE) or abnormal laboratory value which were related to vepdegestrant and assessed as unrelated to mBC, intercurrent illness, or concomitant medications occurring during the first 28 days of treatment that met at least 1 of the study specified criteria.

Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-Related TEAEs

时间窗: From start of study treatment up to 30 days after end of study treatment (up to approximately 4 years and 6 months)

An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness was judged by investigator. Serious AE (SAE) was an AE resulted in any of the following outcomes: death, inpatient hospitalization or prolongation of existing hospitalization; was life-threatening experience (immediate risk of dying); resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was an AE occurring on/after the date of first dose of study medication and within 30 days of the last dose of study medication. TEAEs included both Serious TEAEs and non-serious TEAEs.

Part B: Clinical Benefit Rate (CBR)

时间窗: From start of study treatment until disease progression or death due to any cause (up to approximately 2 years and 11 months)

CBR: percentage of participants with summation of complete response (CR), partial response (PR) or stable disease (SD) of 24 weeks duration or longer. CR: disappearance of all target lesions (TLs) and non-TLs and normalization of tumor marker levels initially above upper limits of normal. PR: \>30% decrease in the sum of the longest diameter (LD) of TLs, taking as reference the baseline sum LD. SD of TLs was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum LD since the treatment started. SD of non-TLs Persistence of one or more non-TLs or/and maintenance of tumor marker level above the normal limits. PD: \>20% increase in the sum of the LD of TLs, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-TLs.

Part C: Number of Participants With Dose Limiting Toxicities (DLTs) During First Cycle of Treatment

时间窗: Baseline (Day 1) up to C1D28

DLT was defined as any AE or abnormal laboratory value which were related to vepdegestrant and assessed as unrelated to mBC, intercurrent illness, or concomitant medications occurring during the first 28 days of treatment that met at least 1 of the study specified criteria.

Part C: Number of Participants With TEAEs, Serious TEAEs and Treatment-Related TEAEs

时间窗: From start of study treatment up to 30 days after end of study treatment (up to approximately 3 years and 9 months)

An AE is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Treatment-related AE was any untoward medical occurrence attributed to study treatment in a participant who received study treatment. Relatedness was judged by investigator. SAE was an AE resulted in any of the following outcomes: death, inpatient hospitalization or prolongation of existing hospitalization; was life-threatening experience (immediate risk of dying); resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect or was otherwise considered medically important. A TEAE was an AE occurring on/after the date of first dose of study medication and within 30 days of the last dose of study medication. TEAEs included both Serious TEAEs and non-serious TEAEs.

Part C: Maximum Tolerated Dose (MTD)

时间窗: Baseline (Day 1) up to C1D28

MTD is the highest dose of a drug that can be given to participants without causing unacceptable DLTs, as determined during a clinical study.

Part A: Incidence of Dose Limiting Toxicities of ARV-471

时间窗: 28 Days

First Cycle Dose limiting toxicities characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug

Part A: Number of Patients with Adverse Events as a measure of safety and tolerability of ARV-471

时间窗: First study drug dose through a minimum of 30 calendar Days After Last study drug administration

Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug.

Part A: Incidence of laboratory abnormalities as a measure of safety and tolerability of ARV-471

时间窗: First study drug dose through a minimum of 30 calendar Days After Last study drug administration

Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing.

Part B: Assessment of anti-tumor activity of ARV-471

时间窗: through study completion, up to approximately 2 years

Clinical benefit response rate based on the summation of CRs, PRs and stable disease of 24 weeks duration or longer

Part C: Incidence of Dose Limiting Toxicities of combination ARV-471 + palbociclib

时间窗: 28 Days

First cycle dose-limiting toxicities and determination of a maximum tolerated dose (MTD) if applicable among the doses evaluated

Part C: Number of Patients with Adverse Events as a measure of safety and tolerability of combination ARV-471 + palbociclib

时间窗: First study drug dose through a minimum of 30 calendar Days After Last study drug administration

Adverse events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study drug combination

Part C: Incidence of laboratory abnormalities as a measure of safety and tolerability of combination ARV-471 + palbociclib

时间窗: First study drug dose through a minimum of 30 calendar Days After Last study drug administration

Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing

次要结局

Part A: Area Under the Concentration-Time Curve During a Dosing Interval (AUCtau) of Vepdegestrant and Its Epimer ARV-473(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1.)
Part A: Disease Control Rate (DCR)(From start of study treatment up to progressive disease or death (up to approximately 4 years and 6 months))
Part A: Area Under the Concentration-time Curve From Time 0 Through the Last Measurable Concentration (AUClast) of Vepdegestrant and Its Epimer ARV-473(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1)
Part A: Maximum Observed Plasma Concentration (Cmax) of Vepdegestrant and Its Epimer ARV-473(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1)
Part A: Minimum Observed Plasma Concentration (Cmin) of Vepdegestrant and Its Epimer ARV- 473(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D15)
Part A: Apparent Oral Plasma Clearance (CL/F) of Vepdegestrant(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D15)
Part A: Time of Maximum Observed Plasma Concentration (Tmax) of Vepdegestrant and Its Epimer ARV- 473(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1)
Part A: Accumulation Ratio for AUC0-tau (Rac [AUCtau]) of Vepdegestrant and Its Epimer ARV- 473(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1)
Part A: Accumulation Ratio for Cmax (Rac [Cmax]) of Vepdegestrant and Its Epimer ARV- 473(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1)
Part A: Effective Half-life Based on Accumulation Ratio of RAUC(0-tau) of Vepdegestrant and Its Epimer ARV-473(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1)
Part A: Epimer (ARV-473) to Parent (Vepdegestrant) Ratio for Cmax (MRCmax).(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1)
Part A: Epimer (ARV-473) to Parent (Vepdegestrant) Ratio for AUCtau (MRAUCtau)(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1)
Part A: Overall Response Rate (ORR) by Investigator Per RECIST v1.1(From start of study treatment until disease progression or death due to any cause (up to approximately 4 years and 6 months))
Part A: Clinical Benefit Rate (CBR)(From start of study treatment until disease progression or death due to any cause (up to approximately 4 years and 6 months))
Part A: Progression-Free Survival (PFS) Per RECIST v1.1(From start of study treatment up to progressive disease or death (up to approximately 4 years and 6 months))
Part A: Duration of Response(From the date of first documented confirmed CR/PR to the date of PD or death due to any cause (up to approximately 4 years and 6 months))
Part B: Overall Response Rate (ORR) by Investigator Per RECIST v1.1(From start of study treatment until disease progression or death due to any cause (up to approximately 2 years and 11 months))
Part B: Progression-Free Survival (PFS) Per RECIST v1.1(From start of study treatment up to progressive disease or death (up to approximately 2 years and 11 months))
Part B: Duration of Response(From the date of first documented confirmed CR/PR to the date of PD or death due to any cause (up to approximately 2 years and 11 months))
Part B: Overall Survival(From start of study treatment up to death (up to approximately 2 years and 11 months))
Part B: Number of Participants With TEAEs, Serious TEAEs and Treatment-Related TEAEs(From start of study treatment up to 30 days after end of study treatment (up to approximately 2 years and 11 months))
Part B: Pre-dose Concentrations of Vepdegestrant and Its Epimer ARV-473(Predose on C1D15 and C1D28 to C26D28)
Part C: Area Under the Concentration-Time Curve During a Dosing Interval (AUCtau) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1 for palbociclib 125 mg arms. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D8, C1D21/C2D15 for palbociclib 100 mg arms.)
Part C: Area Under the Concentration-time Curve From Time 0 Through the Last Measurable Concentration (AUClast) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1 for palbociclib 125 mg arms. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D8, C1D21/C2D15 for palbociclib 100 mg arms.)
Part C: Maximum Observed Plasma Concentration (Cmax) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1 for palbociclib 125 mg arms. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D8, C1D21/C2D15 for palbociclib 100 mg arms.)
Part C: Minimum Observed Plasma Concentration (Cmin) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D15 for arms with palbociclib 125 mg. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D8, C1D21/C2D15 for arm with palbociclib 100 mg.)
Part C: Apparent Oral Plasma Clearance (CL/F) of Vepdegestrant and Palbociclib(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D15 for arms with palbociclib 125 mg. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D8, C1D21/C2D15 for arm with palbociclib 100 mg.)
Part C: Time of Maximum Observed Plasma Concentration (Tmax) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1 for palbociclib 125 mg arms. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D8, C1D21/C2D15 for palbociclib 100 mg arms.)
Part C: Accumulation Ratio for AUC0-tau (Rac [AUCtau]) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1 for palbociclib 125 mg arms.)
Part C: Accumulation Ratio for Cmax (Rac [Cmax]) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1 for palbociclib 125 mg arms.)
Part C: Effective Half-life Based on Accumulation Ratio of RAUC(0-tau) (Effective T1/2) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib(Pre-dose, 1, 2, 4, 6, 8, 12, 24 hours post dose on C1D15 for arms with palbociclib 125 mg (each cycle is of 28 days))
Part C: Epimer (ARV-473) to Parent (Vepdegestrant) Compound Molar Ratio for Cmax (MRCmax)(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1 for palbociclib 125 mg arms. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D21/C2D15 for palbociclib 100 mg arms.)
Part C: Epimer (ARV-473) to Parent (Vepdegestrant) Compound Molar Ratio for AUCtau (MRAUCtau)(Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1 for palbociclib 125 mg arms. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D21/C2D15 for palbociclib 100 mg arms.)
Part C: Overall Response Rate (ORR) by Investigator Per RECIST v1.1(From start of study treatment until disease progression or death due to any cause (up to approximately 3 years and 9 months))
Part C: Clinical Benefit Rate (CBR)(From start of study treatment until disease progression or death due to any cause (up to approximately 3 years and 9 months))
Part C: Progression-Free Survival (PFS) Per RECIST v1.1(From start of study treatment up to progressive disease or death (up to approximately 3 years and 9 months))
Part C: Overall Survival(From start of study treatment up to death (up to approximately 3 years and 9 months))
Part C: Duration of Response(From the date of first documented confirmed CR/PR to the date of PD or death due to any cause (up to approximately 3 years and 9 months))
Part A: Assessment of pharmacokinetic parameter maximum concentration (Cmax).(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471)
Part A: Assessment of pharmacokinetic parameter minimum concentration (Cmin).(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471)
Part A: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax).(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471)
Part B: Evaluation of Plasma Concentrations of ARV-471(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products])
Part C:Assessment of pharmacokinetic parameter area under the concentration-time curve (AUC)(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products)
Part C: Assessment of pharmacokinetic parameter maximum concentration (Cmax).(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products)
Part C: Assessment of pharmacokinetic parameter minimum concentration (Cmin).(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products)
Part C: Assessment of pharmacokinetic parameter time to maximum concentration (Tmax)(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of investigational products)
Part A: Assessment of anti-tumor activity of ARV-471(through study completion, up to approximately 2 years)
Part B: Assessment of anti-tumor activity of ARV-471(through study completion, up to approximately 2 years)
Part B: Evaluation of Safety and Tolerability(First study drug dose through a minimum of 30 calendar Days After Last study drug administration)
Part C: Assessment of anti-tumor activity of ARV-471 in combination with palbociclib(through study completion, up to approximately 2 years)
Part A: Assessment of pharmacokinetic (PK) parameter area under the concentration-time curve (AUC).(At predefined intervals throughout the ARV-471 treatment period, up to approximately 4 weeks after last dose of ARV-471)

试验结果

结果已于 2026-09-29 在 ClinicalTrials.gov 公示。在 ClinicalTrials.gov 查看

受试者流程

入组 89 人 · 完成 0 人

主要终点

Part A: Number of Participants With Dose Limiting Toxicities (DLTs) During First Cycle of Treatment

Participants · 时间窗: Baseline (Day 1) up to C1D28

Part A: Number of Participants With Dose Limiting Toxicities (DLTs) During First Cycle of Treatment
Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=14）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=8）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=22）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=4）
0	0	0	0	0	0	0	0	0

All-Treated Analysis Set.

Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-Related TEAEs

Participants · 时间窗: From start of study treatment up to 30 days after end of study treatment (up to approximately 4 years and 6 months)

Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and Treatment-Related TEAEs
分类	Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=14）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=8）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=22）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=4）
TEAEs	3	3	14	7	7	8	15	21	3
Serious TEAEs	1	1	3	0	0	1	2	2	1
Treatment-Related TEAEs	0	3	14	6	4	6	13	15	2

All-Treated Analysis Set.

Part B: Clinical Benefit Rate (CBR)

percentage of participants · 95% Confidence Interval · 时间窗: From start of study treatment until disease progression or death due to any cause (up to approximately 2 years and 11 months)

Part B: Clinical Benefit Rate (CBR)
Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion) （n=35）	Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion) （n=36）
37.1 (21.5–55.1)	38.9 (23.1–56.5)

The Clinically Evaluable Analysis Set consisted of all participants in the All-Treated analysis set and were either a Responder (best overall response of CR/PR) or a Non-Responder with a potential treatment duration of at least 24 weeks prior to any data cutoff.

Part C: Number of Participants With Dose Limiting Toxicities (DLTs) During First Cycle of Treatment

Participants · 时间窗: Baseline (Day 1) up to C1D28

Part C: Number of Participants With Dose Limiting Toxicities (DLTs) During First Cycle of Treatment
Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg (Initially 180 mg)+Palbociclib 125 mg (Dose Escalation) （n=1）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）
0	0	0

For Part C the DLT Analysis Set included participants from 3 dose escalation arms who received at least 70% of planned doses of both palbociclib and vepdegestrant in C1, and all who received less than 70% of planned doses in C1 who had a DLT. Dose expansion cohorts were excluded from DLT assessments.

Part C: Number of Participants With TEAEs, Serious TEAEs and Treatment-Related TEAEs

Participants · 时间窗: From start of study treatment up to 30 days after end of study treatment (up to approximately 3 years and 9 months)

Part C: Number of Participants With TEAEs, Serious TEAEs and Treatment-Related TEAEs
分类	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=21）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=20）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=17）
TEAEs	2	21	3	20	17
Serious TEAEs	1	8	1	4	6
Vepdegestrant-Related TEAEs	2	16	3	17	14
Palbociclib-Related TEAEs	2	21	3	20	17

All-Treated Analysis Set

Part C: Maximum Tolerated Dose (MTD)

milligram · 时间窗: Baseline (Day 1) up to C1D28

Part C: Maximum Tolerated Dose (MTD)
Part C - Dose Escalation Participants （n=6）
NA

Part C: DLT Analysis Set

Part C - Dose Escalation Participants: No DLTs were identified with vepdegestrant therapy administered in combination with palbociclib. As a result, the MTD for combination therapy was not identified.

其他终点（38）

Part A: Area Under the Concentration-Time Curve During a Dosing Interval (AUCtau) of Vepdegestrant and Its Epimer ARV-473

hour*nanogram per millilter (h*ng/mL) · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1.

Part A: Area Under the Concentration-Time Curve During a Dosing Interval (AUCtau) of Vepdegestrant and Its Epimer ARV-473
分类	Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=13）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=8）	Part A - Phase 1: Vepdegestrant 250 mg （n=7）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 400 mg/300mg （n=2）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=12）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=1）
Vepdegestrant: C1D1	1713.4 (6.5255)	2963.7 (33.364)	3767 (47.941)	6326.2 (21.225)	9580.3 (12.457)	9111.2 (47.687)	—	12172 (32.121)	—	16784 (28.24)	NA (NA)
Vepdegestrant: C1D15	4051.4 (25.594)	7323.7 (15.276)	8009.8 (40.063)	13714 (12.903)	19225 (31.77)	15810 (37.836)	22062 (28.844)	25931 (26.561)	NA (NA)	34585 (35.453)	NA (NA)
ARV-473: C1D1	193.5 (4.0425)	323.47 (36.121)	425.2 (53.143)	673.95 (19.937)	1022.6 (9.9255)	959.2 (43.348)	—	1352.4 (37.377)	—	1795.2 (26.921)	NA (NA)
ARV-473: C1D15	1279.2 (33.1)	2243.2 (8.1246)	2601.4 (42.081)	3973.7 (24.443)	5799.4 (34.407)	5084.6 (38.893)	8086.7 (47.183)	8076.6 (33.749)	NA (NA)	10198 (40.688)	NA (NA)

Pharmacokinetic (PK) Parameter Analysis Set: All-Treated Analysis Set with at least one PK parameter of interest for vepdegestrant /ARV-473. Participants with available data analyzed. For 250 mg BID and 400/300 mg arms, only the predose sample on C1D2 was collected after C1D1 dosing. As dosing interval was 12 hours, the available C1D2 predose sample did not adequately characterize the concentration-time profile over the first dose interval on C1D1, and AUCtau could not be reliably calculated.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 19639 and 19639 respectively.

Part A - Phase 1: Vepdegestrant 400 mg/300mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 14815 and 35360, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 26572 and 26572 respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 2009.3 and 2009.3 respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 7387.4 and 7387.4 respectively.

Part A: Area Under the Concentration-time Curve From Time 0 Through the Last Measurable Concentration (AUClast) of Vepdegestrant and Its Epimer ARV-473

h*ng/mL · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1

Part A: Area Under the Concentration-time Curve From Time 0 Through the Last Measurable Concentration (AUClast) of Vepdegestrant and Its Epimer ARV-473
分类	Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=13）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=8）	Part A - Phase 1: Vepdegestrant 250 mg （n=10）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 400 mg/300 mg （n=3）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=12）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=1）
Vepdegestrant: C1D1	599.09 (19.386)	957.86 (17.068)	1130.4 (108.47)	2060.2 (25.625)	2782.3 (29.217)	2571.9 (43.222)	2924.4 (32.312)	3905.4 (38.53)	3798.6 (101.63)	5820.2 (31.656)	NA (NA)
Vepdegestrant: C1D15	1527.2 (27.151)	2607.6 (8.3221)	2979.6 (45.329)	4831.1 (11.036)	7083.4 (29.436)	5736.7 (37.033)	14833 (25.669)	9382 (27.929)	NA (NA)	12296 (32.053)	NA (NA)
ARV-473: C1D1	39.267 (23.637)	56.59 (20.68)	69.024 (165.07)	122.5 (28.646)	163.56 (38.77)	157.7 (43.521)	178.88 (47.75)	253.86 (38.75)	219.79 (95.555)	361.45 (30.093)	NA (NA)
ARV-473: C1D15	425.26 (35.876)	770.48 (6.2883)	871.9 (48.311)	1311.2 (23.677)	1940.2 (34.569)	1618.9 (36.407)	5384.5 (47.705)	2643 (32.639)	NA (NA)	3335.2 (40.576)	NA (NA)

PK Parameter Analysis Set with available data analyzed.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 6463.2 and 6463.2 respectively.

Part A - Phase 1: Vepdegestrant 400 mg/300 mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 10383 and 23820, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 8628.2 and 8628.2, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 391.69 and 391.69, respectively.

Part A - Phase 1: Vepdegestrant 400 mg/300 mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 2564.6 and 8173.6, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 2360.1 and 2360.1, respectively.

Part A: Maximum Observed Plasma Concentration (Cmax) of Vepdegestrant and Its Epimer ARV-473

ng/mL · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1

Part A: Maximum Observed Plasma Concentration (Cmax) of Vepdegestrant and Its Epimer ARV-473
分类	Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=13）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=8）	Part A - Phase 1: Vepdegestrant 250 mg （n=10）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 400 mg/300 mg （n=3）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=12）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=1）
Vepdegestrant: C1D1	108.88 (5.6696)	194.44 (33.011)	251.04 (40.887)	403.68 (21.071)	591.69 (14.076)	533.64 (52.319)	663.05 (18.043)	748.38 (34.275)	716.2 (130.53)	1046.1 (31.065)	NA (NA)
Vepdegestrant: C1D15	219.21 (26.659)	404.53 (7.6864)	478.28 (41.379)	798.83 (5.7971)	1062.3 (27.301)	882.6 (43.116)	2212.5 (28.604)	1501.6 (26.697)	NA (NA)	1883 (30.568)	NA (NA)
ARV-473: C1D1	11.032 (15.269)	19.748 (43.608)	24.888 (41.355)	39.324 (28.389)	62.344 (12.975)	58.607 (50.927)	51.931 (25.609)	76.925 (44.573)	47.44 (119.4)	98.066 (28.697)	NA (NA)
ARV-473: C1D15	57.645 (31.847)	108.2 (6.0056)	131.26 (44.089)	191.08 (18.518)	273.35 (31.598)	233.57 (36.903)	761.99 (50.623)	381.65 (31.454)	NA (NA)	480.42 (41.513)	NA (NA)

PK Parameter Analysis Set for vepdegestrant or ARV-473 with available data was analyzed.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 1450 and 1450, respectively.

Part A - Phase 1: Vepdegestrant 400 mg/300 mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 1510 and 3360, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 1530 and 1530, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 108 and 108, respectively.

Part A - Phase 1: Vepdegestrant 400 mg/300 mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 378 and 1060, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 325 and 325, respectively.

Part A: Minimum Observed Plasma Concentration (Cmin) of Vepdegestrant and Its Epimer ARV- 473

ng/mL · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D15

Part A: Minimum Observed Plasma Concentration (Cmin) of Vepdegestrant and Its Epimer ARV- 473
分类	Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=13）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=8）	Part A - Phase 1: Vepdegestrant 250 mg （n=10）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 400 mg/300 mg （n=2）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=11）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=1）
Vepdegestrant: C1D15	125.3 (35.121)	207.19 (8.3176)	208.82 (54.16)	380.95 (24.591)	573.38 (44.962)	444.36 (44.201)	1420.8 (27.985)	757.52 (35.202)	NA (NA)	1020.9 (44.61)	NA (NA)
ARV-473: C1D15	48.45 (33.548)	85.191 (1.7834)	83.063 (64.476)	142.73 (31.638)	210.58 (39.478)	174.72 (48.717)	561.84 (43.197)	290.01 (37.161)	NA (NA)	365.46 (41.587)	NA (NA)

PK Parameter Analysis Set for vepdegestrant or ARV-473 with available data was analyzed.

Part A - Phase 1: Vepdegestrant 400 mg/300 mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 992 and 2680, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 681 and 681, respectively.

Part A - Phase 1: Vepdegestrant 400 mg/300 mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 251 and 982, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 280 and 280, respectively.

Part A: Apparent Oral Plasma Clearance (CL/F) of Vepdegestrant

L/h · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D15

Part A: Apparent Oral Plasma Clearance (CL/F) of Vepdegestrant
Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=13）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=6）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 250 mg （n=7）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 400 mg/300 mg （n=2）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=11）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=1）
7.4 (25.6)	8.19 (15.3)	12.5 (40.1)	8.75 (12.9)	9.36 (31.8)	12.7 (37.8)	11.3 (28.8)	13.9 (26.6)	NA (NA)	14.5 (35.5)	NA (NA)

PK Parameter Analysis Set for vepdegestrant with available data was analyzed.

Part A - Phase 1: Vepdegestrant 400 mg/300 mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 11.3 and 27, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 26.3 and 26.3, respectively.

Part A: Time of Maximum Observed Plasma Concentration (Tmax) of Vepdegestrant and Its Epimer ARV- 473

hours · Full Range · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1

Part A: Time of Maximum Observed Plasma Concentration (Tmax) of Vepdegestrant and Its Epimer ARV- 473
分类	Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=13）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=8）	Part A - Phase 1: Vepdegestrant 250 mg （n=10）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 400 mg/300 mg （n=3）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=12）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=1）
Vepdegestrant: C1D1	4.02 (4.00–5.87)	6.02 (4.00–6.10)	5.75 (2.22–26.05)	5.92 (4.03–7.82)	5.98 (4.03–7.82)	5.82 (4.00–7.75)	6.86 (2.00–7.87)	5.83 (3.98–7.78)	4.13 (3.93–5.82)	4.94 (0.95–7.95)	NA (5.75–5.75)
Vepdegestrant: C1D15	4.08 (3.92–6.00)	4.15 (3.95–6.00)	4.25 (1.87–7.98)	5.92 (3.93–7.78)	5.03 (2.08–5.97)	4.05 (3.83–7.80)	5.97 (1.97–7.92)	5.77 (3.92–8.08)	NA (4.10–5.95)	5.92 (3.83–7.78)	NA (5.95–5.95)
ARV-473: C1D1	24.00 (24.00–24.00)	24.00 (24.00–24.00)	24.00 (5.75–26.05)	24.00 (7.67–24.00)	24.00 (24.00–24.00)	24.00 (24.00–24.92)	7.78 (4.00–8.12)	24.00 (24.00–24.00)	7.80 (5.85–7.85)	24.00 (6.05–24.00)	NA (24.00–24.00)
ARV-473: C1D15	6.03 (3.92–7.75)	2.07 (1.02–5.88)	5.97 (0.00–7.98)	6.00 (3.92–7.78)	5.88 (3.92–7.75)	5.75 (1.03–7.85)	4.05 (0.98–7.92)	6.03 (1.98–8.75)	NA (5.88–5.95)	6.00 (3.83–7.80)	NA (7.78–7.78)

PK Parameter Analysis Set for vepdegestrant or ARV-473 with available data was analyzed.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence median data was not evaluable. Therefore, minimum and maximum values are reported.

Part A - Phase 1: Vepdegestrant 400 mg/300 mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the median value was considered insufficient for evaluation. Therefore, minimum and maximum values are reported.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence median data was not evaluable. Therefore, minimum and maximum values are reported.

Part A: Accumulation Ratio for AUC0-tau (Rac [AUCtau]) of Vepdegestrant and Its Epimer ARV- 473

ratio · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1

Part A: Accumulation Ratio for AUC0-tau (Rac [AUCtau]) of Vepdegestrant and Its Epimer ARV- 473
分类	Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=12）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=6）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 250 mg （n=0）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 400 mg/300 mg （n=0）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=11）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=1）
Vepdegestrant	2.36 (21.4)	2.47 (18.8)	2.19 (22.5)	2.17 (18.6)	2.01 (23.1)	1.66 (49.1)	—	2.13 (28.5)	—	2.04 (39.6)	NA (NA)
ARV-473	6.61 (28.8)	6.93 (27.5)	6.14 (30.9)	5.9 (30.4)	5.7 (37.3)	5.19 (49.7)	—	5.97 (33.6)	—	5.66 (48.5)	NA (NA)

PK Parameter Analysis Set for vepdegestrant or ARV-473 with available data was analyzed.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 1.35 and 1.35, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 3.68 and 3.68, respectively.

Part A: Accumulation Ratio for Cmax (Rac [Cmax]) of Vepdegestrant and Its Epimer ARV- 473

ratio · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1

Part A: Accumulation Ratio for Cmax (Rac [Cmax]) of Vepdegestrant and Its Epimer ARV- 473
分类	Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=12）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=6）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 250 mg （n=7）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 400 mg/300 mg （n=2）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=11）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=1）
Vepdegestrant	2.01 (25.9)	2.08 (24.9)	1.99 (27.9)	1.98 (16.4)	1.78 (23.7)	1.57 (56.6)	3.3 (20.3)	2.01 (23.1)	NA (NA)	1.76 (35.6)	NA (NA)
ARV-473	5.23 (22.6)	5.48 (40.6)	5.15 (31.8)	4.86 (28.9)	4.49 (28.8)	3.96 (53.8)	13.7 (52.6)	4.96 (37.9)	NA (NA)	4.93 (50.4)	NA (NA)

PK Parameter Analysis Set for vepdegestrant or ARV-473 with available data was analyzed.

Part A - Phase 1: Vepdegestrant 400 mg/300 mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 2.82 and 6.65, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 1.06 and 1.06, respectively.

Part A - Phase 1: Vepdegestrant 400 mg/300 mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 14.4 and 23.5, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 3.01 and 3.01, respectively.

Part A: Effective Half-life Based on Accumulation Ratio of RAUC(0-tau) of Vepdegestrant and Its Epimer ARV-473

hour · Standard Deviation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1

Part A: Effective Half-life Based on Accumulation Ratio of RAUC(0-tau) of Vepdegestrant and Its Epimer ARV-473
分类	Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=12）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=6）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 250 mg （n=0）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 400 mg/300 mg （n=0）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=11）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=1）
Vepdegestrant	30.8 (8.17)	32.5 (7.57)	28 (8.56)	27.4 (7.5)	24.8 (7.58)	23 (13.4)	—	27.5 (10.8)	—	26.8 (14.6)	NA (NA)
ARV-473	104 (29.9)	110 (30.6)	98.3 (35.9)	93.4 (32.2)	91 (31.5)	86 (42.9)	—	95.6 (32.8)	—	94.9 (47.8)	NA (NA)

PK Parameter Analysis Set for vepdegestrant or ARV-473 with available data was analyzed.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 12.4 and 12.4, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 52.4 and 52.4, respectively.

Part A: Epimer (ARV-473) to Parent (Vepdegestrant) Ratio for Cmax (MRCmax).

ratio · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1

Part A: Epimer (ARV-473) to Parent (Vepdegestrant) Ratio for Cmax (MRCmax).
分类	Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=13）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=8）	Part A - Phase 1: Vepdegestrant 250 mg （n=10）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 400 mg/300 mg （n=3）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=12）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=1）
C1D1	0.101 (17.4)	0.102 (10.9)	0.0991 (24.8)	0.0974 (33)	0.105 (16.6)	0.11 (20.4)	0.0783 (27.3)	0.103 (29.6)	0.0662 (6.85)	0.0937 (20)	NA (NA)
C1D15	0.263 (9.26)	0.267 (7.87)	0.274 (21.5)	0.239 (19.8)	0.257 (17.2)	0.265 (23)	0.344 (30.9)	0.254 (26.9)	NA (NA)	0.255 (26)	NA (NA)

PK Parameter Analysis Set for vepdegestrant or ARV-473 with available data was analyzed.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 0.0745 and 0.0745, respectively.

Part A - Phase 1: Vepdegestrant 400 mg/300 mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 0.25 and 0.315, respectively.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 0.212 and 0.212, respectively.

Part A: Epimer (ARV-473) to Parent (Vepdegestrant) Ratio for AUCtau (MRAUCtau)

ratio · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1

Part A: Epimer (ARV-473) to Parent (Vepdegestrant) Ratio for AUCtau (MRAUCtau)
分类	Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=13）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=8）	Part A - Phase 1: Vepdegestrant 250 mg （n=7）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 400 mg/300 mg （n=2）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=12）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=1）
C1D1	0.113 (3.42)	0.109 (3.13)	0.113 (12.9)	0.107 (13.9)	0.107 (10.9)	0.105 (16.8)	—	0.111 (16.1)	—	0.107 (7.79)	NA (NA)
C1D15	0.316 (9.83)	0.306 (7.59)	0.325 (21)	0.29 (17.3)	0.302 (13.9)	0.322 (14.7)	0.367 (27.8)	0.311 (15.2)	NA (NA)	0.295 (18.5)	NA (NA)

PK Parameter Analysis Set for vepdegestrant or ARV-473 with available data was analyzed. For 250 mg BID and 400/300 mg arms, only the predose sample on C1D2 was collected after C1D1 dosing. As dosing interval was 12 hours, the available C1D2 predose sample did not adequately characterize the concentration-time profile over the first dose interval on C1D1, and AUCtau could not be reliably calculated.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Only 1 participant was analyzed, hence data was not evaluable. Therefore, minimum and maximum values are reported as 0.102 and 0.102, respectively.

Part A - Phase 1: Vepdegestrant 400 mg/300 mg: For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 0.256 and 0.349, respectively.

Part A: Overall Response Rate (ORR) by Investigator Per RECIST v1.1

percentage of participants · 95% Confidence Interval · 时间窗: From start of study treatment until disease progression or death due to any cause (up to approximately 4 years and 6 months)

Part A: Overall Response Rate (ORR) by Investigator Per RECIST v1.1
Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=2）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=12）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=5）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=6）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=11）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=18）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=1）
0 (0.0–70.8)	0 (0.0–84.2)	25.0 (5.5–57.2)	20.0 (0.5–71.6)	0 (0.0–45.9)	14.3 (0.4–57.9)	18.2 (2.3–51.8)	5.6 (0.1–27.3)	0 (0.0–97.5)

All Treated Analysis Set with measurable disease at baseline were included in the analysis.

Part A: Clinical Benefit Rate (CBR)

percentage of participants · 95% Confidence Interval · 时间窗: From start of study treatment until disease progression or death due to any cause (up to approximately 4 years and 6 months)

Part A: Clinical Benefit Rate (CBR)
Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=14）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=8）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=22）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=4）
33.3 (0.8–90.6)	33.3 (0.8–90.6)	42.9 (17.7–71.1)	71.4 (29.0–96.3)	14.3 (0.4–57.9)	12.5 (0.3–52.7)	40.0 (16.3–67.7)	31.8 (13.9–54.9)	50.0 (6.8–93.2)

Clinically Evaluable Analysis Set.

Part A: Disease Control Rate (DCR)

percentage of participants · 95% Confidence Interval · 时间窗: From start of study treatment up to progressive disease or death (up to approximately 4 years and 6 months)

Part A: Disease Control Rate (DCR)
Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=13）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=6）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=8）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=19）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=4）
33.3 (0.8–90.6)	33.3 (0.8–90.6)	61.5 (31.6–86.1)	85.7 (42.1–99.6)	50.0 (11.8–88.2)	25.0 (3.2–65.1)	73.3 (44.9–92.2)	47.4 (24.4–71.1)	50.0 (6.8–93.2)

The Disease Response Analysis Set consisted of all participants in the All-Treated Analysis Set with baseline and at least 1 post-baseline radiographic assessment (computed tomography \[CT\] or magnetic resonance imaging \[MRI\] scan).

Part A: Progression-Free Survival (PFS) Per RECIST v1.1

months · 95% Confidence Interval · 时间窗: From start of study treatment up to progressive disease or death (up to approximately 4 years and 6 months)

Part A: Progression-Free Survival (PFS) Per RECIST v1.1
Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=14）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=7）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=8）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=15）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=22）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=4）
NA (NA–NA)	NA (NA–NA)	NA (NA–NA)	NA (NA–NA)	NA (NA–NA)	NA (NA–NA)	NA (NA–NA)	NA (NA–NA)	NA (NA–NA)

All-Treated Analysis Set.

Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A: Duration of Response

months · 95% Confidence Interval · 时间窗: From the date of first documented confirmed CR/PR to the date of PD or death due to any cause (up to approximately 4 years and 6 months)

Part A: Duration of Response
Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation) （n=0）	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation) （n=0）	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation) （n=3）	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation) （n=1）	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation) （n=0）	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation) （n=1）	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation) （n=2）	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation) （n=1）	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation) （n=0）
—	—	NA (NA–NA)	NA (NA–NA)	—	NA (NA–NA)	NA (NA–NA)	NA (NA–NA)	—

Disease Response Analysis Set with first documented confirmed CR/PR was analyzed.

Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation): Median and 95% CI could not be estimated due to insufficient number of participants with events.

Part B: Overall Response Rate (ORR) by Investigator Per RECIST v1.1

percentage of participants · 95% Confidence Interval · 时间窗: From start of study treatment until disease progression or death due to any cause (up to approximately 2 years and 11 months)

Part B: Overall Response Rate (ORR) by Investigator Per RECIST v1.1
Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion) （n=24）	Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion) （n=21）
8.3 (1.0–27.0)	14.3 (3.0–36.3)

Disease Response Analysis Set with measurable disease at baseline were included in the analysis of ORR.

Part B: Progression-Free Survival (PFS) Per RECIST v1.1

months · 95% Confidence Interval · 时间窗: From start of study treatment up to progressive disease or death (up to approximately 2 years and 11 months)

Part B: Progression-Free Survival (PFS) Per RECIST v1.1
Part B - Phase 2: Vepdegestrant 200 mg (Cohort Expansion) （n=35）	Part B - Phase 2: Vepdegestrant 500 mg (Cohort Expansion) （n=36）
3.5 (1.8–7.8)	5.4 (1.9–8.8)

All-Treated Analysis Set

Part B: Duration of Response

months · 95% Confidence Interval · 时间窗: From the date of first documented confirmed CR/PR to the date of PD or death due to any cause (up to approximately 2 years and 11 months)

Part B: Duration of Response
Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion) （n=2）	Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion) （n=3）
10.4 (3.7–NA)	7.6 (5.7–NA)

Disease Response Analysis Set with first documented confirmed CR/PR was analyzed.

Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion): Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.

Part B: Overall Survival

months · 95% Confidence Interval · 时间窗: From start of study treatment up to death (up to approximately 2 years and 11 months)

Part B: Overall Survival
Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion) （n=35）	Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion) （n=36）
NA (27.6–NA)	NA (19.7–NA)

All-Treated Analysis Set

Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion): Median and Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Median and Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.

Part B: Number of Participants With TEAEs, Serious TEAEs and Treatment-Related TEAEs

Participants · 时间窗: From start of study treatment up to 30 days after end of study treatment (up to approximately 2 years and 11 months)

Part B: Number of Participants With TEAEs, Serious TEAEs and Treatment-Related TEAEs
分类	Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion) （n=35）	Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion) （n=36）
TEAEs	32	34
Serious TEAEs	6	5
Treatment-Related TEAEs	30	27

All-Treated Analysis Set

Part B: Pre-dose Concentrations of Vepdegestrant and Its Epimer ARV-473

ng/mL · Standard Deviation · 时间窗: Predose on C1D15 and C1D28 to C26D28

Part B: Pre-dose Concentrations of Vepdegestrant and Its Epimer ARV-473
分类	Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion) （n=29）	Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion) （n=33）
Vepdegestrant: C1D15	603.621 (422.4487)	956.692 (403.4008)
Vepdegestrant: C1D28	637.783 (323.5315)	1030.000 (590.7248)
Vepdegestrant: C2D28	527.143 (273.8017)	839.313 (405.5787)
Vepdegestrant: C3D28	524.067 (236.7164)	981.538 (457.8516)
Vepdegestrant: C4D28	525.727 (268.2164)	918.532 (464.2570)
Vepdegestrant: C5D28	534.364 (245.3232)	1148.100 (690.3299)
Vepdegestrant: C6D28	501.000 (302.0592)	984.000 (417.0430)
Vepdegestrant: C7D28	444.444 (179.8285)	957.333 (542.0904)
Vepdegestrant: C8D28	473.036 (282.8287)	895.000 (383.0244)
Vepdegestrant: C9D28	387.500 (129.3922)	1043.250 (288.6328)
Vepdegestrant: C10D28	436.500 (133.7223)	1216.400 (638.9502)
Vepdegestrant: C11D28	404.000 (210.0286)	1128.400 (427.0162)
Vepdegestrant: C12D28	410.000 (NA)	1175.500 (445.2277)
Vepdegestrant: C13D28	504.000 (224.3056)	974.000 (588.0034)
Vepdegestrant: C14D28	510.000 (222.0833)	1134.000 (341.2096)
Vepdegestrant: C15D28	423.250 (244.6853)	940.500 (547.7283)
Vepdegestrant: C16D28	451.750 (184.9709)	1111.500 (536.1129)
Vepdegestrant: C17D28	488.500 (162.4346)	1003.500 (601.5538)
Vepdegestrant: C18D28	477.667 (355.3594)	1163.500 (NA)
Vepdegestrant: C19D28	303.500 (NA)	1226.500 (NA)
Vepdegestrant: C20D28	468.000 (NA)	382.000 (NA)
Vepdegestrant: C21D28	383.500 (NA)	519.000 (NA)
Vepdegestrant: C22D28	666.000 (NA)	470.000 (NA)
Vepdegestrant: C23D28	446.000 (NA)	408.000 (NA)
Vepdegestrant: C24D28	—	536.000 (NA)
Vepdegestrant: C25D28	—	463.000 (NA)
Vepdegestrant: C26D28	—	549.000 (NA)
ARV-473: C1D15	245.43 (162.212)	361.58 (166.885)
ARV-473: C1D28	272.78 (151.084)	382.32 (242.746)
ARV-473: C2D28	219.26 (118.820)	311.88 (144.295)
ARV-473: C3D28	206.77 (106.138)	349.85 (149.663)
ARV-473: C4D28	187.34 (97.274)	363.97 (184.902)
ARV-473: C5D28	199.14 (86.539)	410.60 (200.839)
ARV-473: C6D28	175.32 (93.520)	348.38 (142.711)
ARV-473: C7D28	180.06 (82.097)	348.44 (172.105)
ARV-473: C8D28	184.99 (112.859)	332.43 (153.503)
ARV-473: C9D28	143.48 (63.649)	309.50 (109.061)
ARV-473: C10D28	175.25 (40.599)	401.60 (171.221)
ARV-473: C11D28	147.57 (67.260)	376.20 (131.665)
ARV-473: C12D28	158.50 (NA)	416.75 (169.567)
ARV-473: C13D28	178.83 (76.819)	341.00 (177.085)
ARV-473: C14D28	185.00 (75.439)	437.00 (103.766)
ARV-473: C15D28	153.35 (64.547)	337.75 (168.300)
ARV-473: C16D28	175.25 (61.711)	392.50 (159.475)
ARV-473: C17D28	172.00 (78.456)	364.00 (187.729)
ARV-473: C18D28	182.67 (143.309)	393.50 (NA)
ARV-473: C19D28	125.50 (NA)	406.00 (NA)
ARV-473: C20D28	189.00 (NA)	165.00 (NA)
ARV-473: C21D28	181.50 (NA)	222.00 (NA)
ARV-473: C22D28	263.00 (NA)	203.00 (NA)
ARV-473: C23D28	181.00 (NA)	169.00 (NA)
ARV-473: C24D28	—	214.00 (NA)
ARV-473: C25D28	—	221.00 (NA)
ARV-473: C26D28	—	219.00 (NA)

PK Pre-Dose Concentration Analysis Set included all participants in All-Treated Analysis Set with at least one evaluable Ctrough following treatment for vepdegestrant/ARV-473. Participants with available data were analyzed.

Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion): For time points with fewer than 3 evaluable participants / less than 50% available observations, the standard deviation (SD) was considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 359.00 and 461.00, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): For time points with fewer than 3 evaluable participants / less than 50% available observations, the SD was considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 427.00 and 1900.00, respectively.

Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion): For time points with fewer than 3 evaluable participants / less than 50% available observations, the SD was considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 172.00 and 435.00, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): For time points with fewer than 3 evaluable participants / less than 50% available observations, SD was considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 443.00 and 2010.00, respectively.

Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 468.00 and 468.00, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 382.00 and 382.00, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 519.00 and 519.00, respectively.

Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 666.00 and 666.00, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 470.00 and 470.00, respectively.

Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 446.00 and 446.00, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 408.00 and 408.00, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 536.00 and 536.00, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 463.00 and 463.00, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 549.00 and 549.00, respectively.

Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 189.0 and 189.0, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 165.0 and 165.0, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 222.0 and 222.0, respectively.

Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 263.0 and 263.0, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 203.0 and 203.0, respectively.

Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 181.0 and 181.0, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 169.0 and 169.0, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 214.0 and 214.0, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 221.0 and 221.0, respectively.

Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion): Only 1 participant was analyzed, hence SD was not evaluable. Therefore, minimum and maximum values are reported as 219.0 and 219.0, respectively.

Part C: Area Under the Concentration-Time Curve During a Dosing Interval (AUCtau) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib

h*ng/mL · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1 for palbociclib 125 mg arms. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D8, C1D21/C2D15 for palbociclib 100 mg arms.

Part C: Area Under the Concentration-Time Curve During a Dosing Interval (AUCtau) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib
分类	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=20）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=20）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=14）
Vepdegestrant: C1D1	NA (NA)	7779.7 (42.146)	14900 (27.65)	16133 (29.712)	—
Vepdegestrant: C1D15	NA (NA)	18416 (46.658)	21522 (8.0698)	33367 (37.641)	—
Vepdegestrant: C1D21/C2D15	—	—	—	—	14216 (36.696)
ARV-473: C1D1	NA (NA)	931.33 (41.933)	1402.6 (35.953)	1833.1 (28.576)	—
ARV-473: C1D15	NA (NA)	6905.6 (57.501)	6598.7 (10.195)	11893 (44.365)	—
ARV-473: C1D21/C2D15	—	—	—	—	5186.3 (49.384)
Palbociclib: C1D1	—	907.67 (31.759)	NA (NA)	819.86 (51.572)	—
Palbociclib: C1D8	—	—	—	—	1742.9 (33.966)
Palbociclib: C1D15	—	2902.9 (45.744)	2571.1 (16.821)	2992.1 (39.59)	—
Palbociclib: C1D21/C2D15	—	—	—	—	1804.9 (42.571)

PK Parameter Analysis Set for vepdegestrant/ARV-473/palbociclib with available data was analyzed. Palbociclib was validated in K2EDTA plasma; PK samples from the vepdegestrant 180 mg + palbociclib 125 mg cohort were collected in lithium heparin tubes, precluding analysis/PK estimation, resulting in n=0 for this cohort. In the vepdegestrant 200 mg + palbociclib 100 mg cohort, only a predose sample was collected on C1D15; steady-state PK was assessed on C1D21, resulting in n=0 for C1D15.

Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation): For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 4708 and 10055, respectively.

Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation): For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 584.46 and 965.01, respectively.

Part C: Area Under the Concentration-time Curve From Time 0 Through the Last Measurable Concentration (AUClast) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib

Part C: Area Under the Concentration-time Curve From Time 0 Through the Last Measurable Concentration (AUClast) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib
分类	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=21）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=20）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=14）
Vepdegestrant: C1D1	NA (NA)	2351.2 (60.658)	3864.9 (25.629)	4754.7 (46.211)	—
Vepdegestrant: C1D15	NA (NA)	6493.1 (45.981)	8274.6 (20.539)	11378 (43.389)	—
Vepdegestrant: C1D21/C2D15	—	—	—	—	4940.9 (38.306)
ARV-473: C1D1	NA (NA)	165.52 (64.373)	221.05 (28.37)	316.86 (52.866)	—
ARV-473: C1D15	NA (NA)	2273.9 (53.045)	2252 (14.983)	3730.6 (47.654)	—
ARV-473: C1D21/C2D15	—	—	—	—	1693.5 (49.814)
Palbociclib: C1D1	—	253.98 (63.902)	NA (NA)	219.28 (133.03)	—
Palbociclib: C1D8	—	—	—	—	620.4 (36.956)
Palbociclib: C1D15	—	987.34 (45.683)	848.43 (21.093)	929.8 (59.414)	—
Palbociclib: C1D21/C2D15	—	—	—	—	597.88 (42.112)

PK Parameter Analysis Set for vepdegestrant, ARV-473 or palbociclib with available data was analyzed. Palbociclib was validated in K2EDTA plasma; PK samples from the vepdegestrant 180 mg + palbociclib 125 mg cohort were collected in lithium heparin tubes, precluding analysis/PK estimation, resulting in n=0 for this cohort. In the vepdegestrant 200 mg + palbociclib 100 mg cohort, only a predose sample was collected on C1D15; steady-state PK was assessed on C1D21, resulting in n=0 for C1D15.

Part C: Maximum Observed Plasma Concentration (Cmax) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib

ng/mL · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1 for palbociclib 125 mg arms. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D8, C1D21/C2D15 for palbociclib 100 mg arms.

Part C: Maximum Observed Plasma Concentration (Cmax) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib
分类	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=21）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=20）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=14）
Vepdegestrant: C1D1	NA (NA)	506.3 (40.74)	972.26 (22.31)	980.86 (36.161)	—
Vepdegestrant: C1D15	NA (NA)	1046.4 (44.632)	1347.8 (14.133)	1795.5 (36.661)	—
Vepdegestrant: C1D21/C2D15	—	—	—	—	790.6 (35.141)
ARV-473: C1D1	NA (NA)	56.054 (35.146)	87.066 (24.59)	105.15 (32.657)	—
ARV-473: C1D15	NA (NA)	336.12 (55.493)	334.13 (19.859)	576.82 (48.933)	—
ARV-473: C1D21/C2D15	—	—	—	—	238.23 (47.27)
Palbociclib: C1D1	—	59.851 (32.502)	NA (NA)	59.453 (56.309)	—
Palbociclib: C1D8	—	—	—	—	98.171 (39.202)
Palbociclib: C1D15	—	153.42 (45.26)	127.46 (26.185)	155.53 (39.057)	—
Palbociclib: C1D21/C2D15	—	—	—	—	95.999 (32.041)

Part C: Minimum Observed Plasma Concentration (Cmin) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib

ng/mL · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D15 for arms with palbociclib 125 mg. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D8, C1D21/C2D15 for arm with palbociclib 100 mg.

Part C: Minimum Observed Plasma Concentration (Cmin) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib
分类	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=18）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=16）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=12）
Vepdegestrant: C1D15	NA (NA)	472.59 (81.959)	637.02 (7.9382)	1102.3 (42.598)	—
Vepdegestrant: C1D21/C2D15	—	—	—	—	420.7 (43.572)
ARV-473: C1D15	NA (NA)	199.89 (88.088)	245.71 (8.7464)	437.29 (42.344)	—
ARV-473: C1D21/C2D15	—	—	—	—	189.86 (51.056)
Palbociclib: C1D8	—	—	—	—	51.963 (39.374)
Palbociclib: C1D15	—	91.821 (48.474)	88.771 (10.076)	96.593 (46.645)	—
Palbociclib: C1D21/C2D15	—	—	—	—	NA (NA)

Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion): For time points with fewer than 3 evaluable participants / less than 50% available observations, the geometric mean and coefficient of variation were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 13 and 31.9, respectively.

Part C: Apparent Oral Plasma Clearance (CL/F) of Vepdegestrant and Palbociclib

L/h · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D15 for arms with palbociclib 125 mg. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D8, C1D21/C2D15 for arm with palbociclib 100 mg.

Part C: Apparent Oral Plasma Clearance (CL/F) of Vepdegestrant and Palbociclib
分类	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=18）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=15）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=14）
Vepdegestrant: C1D15	NA (NA)	10.9 (46.7)	18.6 (8.07)	15 (37.6)	—
Vepdegestrant: C1D21/C2D15	—	—	—	—	14.1 (36.7)
Palbociclib: C1D8	—	—	—	—	56.2 (35)
Palbociclib: C1D15	—	43.1 (45.7)	48.6 (16.8)	41.8 (39.6)	—
Palbociclib: C1D21/C2D15	—	—	—	—	55.4 (42.6)

Part C: Time of Maximum Observed Plasma Concentration (Tmax) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib

hour · Full Range · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1 for palbociclib 125 mg arms. Pre-dose, 1, 2, 4, 6, 8 hours post dose on C1D8, C1D21/C2D15 for palbociclib 100 mg arms.

Part C: Time of Maximum Observed Plasma Concentration (Tmax) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib
分类	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=21）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=20）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=14）
Vepdegestrant: C1D1	NA (6.00–6.02)	5.83 (1.92–23.92)	7.78 (6.07–7.90)	5.94 (1.85–7.80)	—
Vepdegestrant: C1D15	NA (4.03–4.07)	4.08 (2.00–8.08)	5.92 (3.98–6.03)	4.09 (2.03–7.75)	—
Vepdegestrant: C1D21/C2D15	—	—	—	—	5.96 (3.83–7.78)
ARV-473: C1D1	NA (21.83–23.10)	23.72 (5.83–28.83)	23.98 (21.13–25.15)	23.65 (7.78–27.48)	—
ARV-473: C1D15	NA (4.03–8.03)	7.77 (1.03–8.08)	5.92 (3.98–6.03)	4.14 (0.00–8.00)	—
ARV-473: C1D21/C2D15	—	—	—	—	5.91 (3.83–7.87)
Palbociclib: C1D1	—	6.10 (1.95–8.13)	NA (6.07–7.78)	5.98 (1.83–27.48)	—
Palbociclib: C1D8	—	—	—	—	5.96 (1.00–7.92)
Palbociclib: C1D15	—	5.93 (0.00–8.08)	5.92 (2.03–6.03)	5.03 (0.00–7.92)	—
Palbociclib: C1D21/C2D15	—	—	—	—	6.00 (0.93–7.78)

Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation): For time points with fewer than 3 evaluable participants / less than 50% available observations, the median value was considered insufficient for evaluation. Therefore, minimum and maximum values are reported.

Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation): For time points with fewer than 3 evaluable participants / less than 50% available observations, the median value was considered insufficient for evaluation. Therefore, minimum and maximum values are reported.

Part C: Accumulation Ratio for AUC0-tau (Rac [AUCtau]) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib

ratio · Geometric Coefficient of Variation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12 (optional) hours post dose on C1D1 and C1D15, and an additional sample at 24 hours post dose on C1D1 for palbociclib 125 mg arms.

Part C: Accumulation Ratio for AUC0-tau (Rac [AUCtau]) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib
分类	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=17）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=15）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=0）
Vepdegestrant	NA (NA)	2.29 (37.2)	1.44 (27.2)	2.05 (28.5)	—
ARV-473	NA (NA)	7.2 (40.2)	4.7 (37.3)	6.43 (37.2)	—
Palbociclib	—	2.92 (16)	NA (NA)	3.47 (41.7)	—

PK Parameter Analysis Set for vepdegestrant, ARV-473 or palbociclib with available data was analyzed.

Part C: Accumulation Ratio for Cmax (Rac [Cmax]) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib

Part C: Accumulation Ratio for Cmax (Rac [Cmax]) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib
分类	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=18）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=26）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=0）
Vepdegestrant	NA (NA)	1.96 (40.8)	1.39 (14.5)	1.79 (23.6)	—
ARV-473	NA (NA)	5.86 (32)	3.84 (31.8)	5.39 (39.5)	—
Palbociclib	—	2.44 (24.4)	NA (NA)	2.74 (48.2)	—

PK Parameter Analysis Set for vepdegestrant, ARV-473 or palbociclib with available data was analyzed.

Part C: Effective Half-life Based on Accumulation Ratio of RAUC(0-tau) (Effective T1/2) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib

hours · Standard Deviation · 时间窗: Pre-dose, 1, 2, 4, 6, 8, 12, 24 hours post dose on C1D15 for arms with palbociclib 125 mg (each cycle is of 28 days)

Part C: Effective Half-life Based on Accumulation Ratio of RAUC(0-tau) (Effective T1/2) of Vepdegestrant, Its Epimer ARV-473 and Palbociclib
分类	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=17）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=15）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=0）
Vepdegestrant	NA (NA)	31.2 (15.3)	14.5 (7.59)	25.9 (9.91)	—
ARV-473	NA (NA)	120 (48.3)	73.2 (31.6)	104 (37)	—
Palbociclib	—	40.2 (7.65)	NA (NA)	53.7 (28.8)	—

PK Parameter Analysis Set for vepdegestrant, 473 or palbociclib with available data was analyzed.

Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation): For time points with fewer than 3 evaluable participants / less than 50% available observations, the mean and SD were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 23.8 and 41.9, respectively.

Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation): For time points with fewer than 3 evaluable participants / less than 50% available observations, the mean and SD were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 93.3 and 188, respectively.

Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation): For time points with fewer than 3 evaluable participants / less than 50% available observations, the mean and SD were considered insufficient for evaluation. Therefore, minimum and maximum values are reported as 44.7 and 55.8, respectively.

Part C: Epimer (ARV-473) to Parent (Vepdegestrant) Compound Molar Ratio for Cmax (MRCmax)

Part C: Epimer (ARV-473) to Parent (Vepdegestrant) Compound Molar Ratio for Cmax (MRCmax)
分类	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=21）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=20）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=12）
C1D1	NA (NA)	0.111 (33.3)	0.0896 (3.39)	0.107 (25.4)	—
C1D15	NA (NA)	0.321 (25.9)	0.248 (13.5)	0.321 (30.3)	—
C1D21/C2D15	—	—	—	—	0.301 (22.1)

PK Parameter Analysis Set for vepdegestrant, ARV-473 or palbociclib with available data was analyzed. In the vepdegestrant 200 mg + palbociclib 100 mg cohort, only a predose sample was collected on C1D15; steady-state PK was assessed on C1D21, resulting in n=0 for C1D15.

Part C: Epimer (ARV-473) to Parent (Vepdegestrant) Compound Molar Ratio for AUCtau (MRAUCtau)

Part C: Epimer (ARV-473) to Parent (Vepdegestrant) Compound Molar Ratio for AUCtau (MRAUCtau)
分类	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=20）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=20）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=12）
C1D1	NA (NA)	0.12 (17.3)	0.0941 (9.21)	0.114 (12.1)	—
C1D15	NA (NA)	0.375 (22.1)	0.307 (2.12)	0.356 (15.2)	—
C1D21/C2D15	—	—	—	—	0.365 (19.2)

Part C: Overall Response Rate (ORR) by Investigator Per RECIST v1.1

percentage of participants · 95% Confidence Interval · 时间窗: From start of study treatment until disease progression or death due to any cause (up to approximately 3 years and 9 months)

Part C: Overall Response Rate (ORR) by Investigator Per RECIST v1.1
Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=1）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=15）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=1）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=14）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=7）
0 (0.0–97.5)	53.3 (26.6–78.7)	0 (0.0–97.5)	35.7 (12.8–64.9)	14.3 (0.4–57.9)

Disease Response Analysis Set with measurable disease at baseline were included in the analysis.

Part C: Clinical Benefit Rate (CBR)

percentage of participants · 95% Confidence Interval · 时间窗: From start of study treatment until disease progression or death due to any cause (up to approximately 3 years and 9 months)

Part C: Clinical Benefit Rate (CBR)
Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=21）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=20）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=17）
100 (15.8–100.0)	66.7 (43.0–85.4)	100 (29.2–100)	50.0 (27.2–72.8)	29.4 (10.3–56.0)

Clinically Evaluable Analysis Set

Part C: Progression-Free Survival (PFS) Per RECIST v1.1

months · 95% Confidence Interval · 时间窗: From start of study treatment up to progressive disease or death (up to approximately 3 years and 9 months)

Part C: Progression-Free Survival (PFS) Per RECIST v1.1
Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=21）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=20）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=17）
11.1 (11.1–NA)	13.9 (8.0–19.3)	NA (23.1–NA)	5.6 (3.6–13.7)	3.7 (2.1–8.5)

All-Treated Analysis Set

Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation): Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.

Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation): Median and Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.

Part C: Overall Survival

months · 95% Confidence Interval · 时间窗: From start of study treatment up to death (up to approximately 3 years and 9 months)

Part C: Overall Survival
Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=2）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=21）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=3）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=20）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=17）
NA (NA–NA)	28.4 (26.9–NA)	NA (28.3–NA)	23.4 (8.3–NA)	NA (6.8–NA)

All-Treated Analysis Set

Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation): Median, Lower limit and Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.

Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion): Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.

Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation): Median and Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.

Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion): Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.

Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion): Median and Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.

Part C: Duration of Response

months · 95% Confidence Interval · 时间窗: From the date of first documented confirmed CR/PR to the date of PD or death due to any cause (up to approximately 3 years and 9 months)

Part C: Duration of Response
Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation) （n=0）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion) （n=8）	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation) （n=0）	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion) （n=5）	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion) （n=1）
—	14.6 (4.5–15.9)	—	13.8 (9.5–NA)	6.6 (NA–NA)

Disease Response Analysis Set with first documented confirmed CR/PR was analyzed.

Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion): Upper limit of 95% CI could not be estimated due to insufficient number of participants with events.

Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion): Upper and Lower limit of 95% CI could not be estimated due to insufficient number of participants with events.

安全性

安全性
组别	严重不良事件	死亡
Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation)	1 / 3	2 / 3
Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation)	1 / 3	0 / 3
Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation)	3 / 14	4 / 15
Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation)	0 / 7	5 / 7
Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation)	0 / 7	5 / 7
Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation)	1 / 8	4 / 8
Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation)	2 / 15	7 / 15
Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation)	2 / 22	15 / 22
Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation)	1 / 4	2 / 4
Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion)	6 / 35	12 / 35
Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion)	5 / 36	14 / 36
Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation)	1 / 2	0 / 2
Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion)	8 / 21	6 / 21
Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation)	1 / 3	1 / 3
Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion)	4 / 20	13 / 21
Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion)	6 / 17	4 / 17

最常见的严重不良事件（人数）

最常见的严重不良事件（人数）
事件	Part A - Phase 1: Vepdegestrant 30 mg (Dose Escalation)	Part A - Phase 1: Vepdegestrant 60 mg (Dose Escalation)	Part A - Phase 1: Vepdegestrant 100 mg (Dose Escalation)	Part A - Phase 1: Vepdegestrant 120 mg (Dose Escalation)	Part A - Phase 1: Vepdegestrant 180 mg (Dose Escalation)	Part A - Phase 1: Vepdegestrant 200 mg (Dose Escalation)	Part A - Phase 1: Vepdegestrant 360 mg (Dose Escalation)	Part A - Phase 1: Vepdegestrant 500 mg (Dose Escalation)	Part A - Phase 1: Vepdegestrant 700 mg (Dose Escalation)	Part B - Phase 2: Vepdegestrant 200 mg (Dose Expansion)	Part B - Phase 2: Vepdegestrant 500 mg (Dose Expansion)	Part C - Phase 1b: Vepdegestrant 180 mg+ Palbociclib 125 mg (Dose Escalation)	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 125 mg (Dose Expansion)	Part C - Phase 1b: Vepdegestrant 400 mg + Palbociclib 125 mg (Dose Escalation)	Part C - Phase 1b: Vepdegestrant 500 mg + Palbociclib 125 mg (Dose Expansion)	Part C - Phase 1b: Vepdegestrant 200 mg + Palbociclib 100 mg (Dose Expansion)
Dyspnoea	0 / 3	0 / 3	0 / 14	0 / 7	0 / 7	0 / 8	0 / 15	0 / 22	0 / 4	0 / 35	0 / 36	0 / 2	2 / 21	0 / 3	0 / 20	1 / 17
Ascites	0 / 3	0 / 3	0 / 14	0 / 7	0 / 7	0 / 8	0 / 15	0 / 22	0 / 4	0 / 35	0 / 36	0 / 2	0 / 21	0 / 3	0 / 20	2 / 17
Cerebrovascular accident	0 / 3	0 / 3	0 / 14	0 / 7	0 / 7	0 / 8	0 / 15	0 / 22	0 / 4	0 / 35	0 / 36	0 / 2	2 / 21	0 / 3	0 / 20	0 / 17
Cardiac arrest	0 / 3	0 / 3	0 / 14	0 / 7	0 / 7	0 / 8	0 / 15	1 / 22	0 / 4	0 / 35	0 / 36	0 / 2	0 / 21	0 / 3	0 / 20	0 / 17
Pericardial effusion	0 / 3	0 / 3	1 / 14	0 / 7	0 / 7	0 / 8	0 / 15	0 / 22	0 / 4	0 / 35	0 / 36	0 / 2	0 / 21	0 / 3	0 / 20	0 / 17
Colitis	0 / 3	0 / 3	0 / 14	0 / 7	0 / 7	1 / 8	0 / 15	0 / 22	0 / 4	0 / 35	0 / 36	0 / 2	0 / 21	0 / 3	0 / 20	0 / 17
Dysphagia	0 / 3	0 / 3	0 / 14	0 / 7	0 / 7	0 / 8	0 / 15	0 / 22	0 / 4	0 / 35	0 / 36	0 / 2	0 / 21	0 / 3	1 / 20	0 / 17
Stomatitis	0 / 3	0 / 3	0 / 14	0 / 7	0 / 7	1 / 8	0 / 15	0 / 22	0 / 4	0 / 35	0 / 36	0 / 2	0 / 21	0 / 3	0 / 20	0 / 17
Lung infection	0 / 3	0 / 3	1 / 14	0 / 7	0 / 7	0 / 8	0 / 15	0 / 22	0 / 4	0 / 35	0 / 36	0 / 2	0 / 21	0 / 3	1 / 20	0 / 17
Pneumonia	0 / 3	0 / 3	1 / 14	0 / 7	0 / 7	0 / 8	0 / 15	0 / 22	0 / 4	0 / 35	0 / 36	0 / 2	1 / 21	0 / 3	0 / 20	0 / 17

文档

数值为申办方在 ClinicalTrials.gov 公示的原始数据，未经重新计算；括号内为公示的离散度（如 95% 置信区间）。

研究者

发起方

Arvinas Estrogen Receptor, Inc.

申办方类型

企业

责任方

申办方

研究点 (16)

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标识符

NCT 编号: NCT04072952
其他研究编号: ARV-471-mBC-101, C4891019

日期

首次提交: 2019年8月27日 (7年前)
首次发布: 2019年8月28日 (7年前)
主要完成日期: 2024年9月13日 (2年前)
研究完成日期: 2026年3月5日 (6个月前)
最近核实: 2026年9月1日 (29天前)
最近更新: 2026年9月29日 (昨天)

监管与共享

FDA 监管药物: 是
FDA 监管器械: 否
个体参与者数据共享计划: 否
是否有结果: 是

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