A PHASE 3, RANDOMIZED, OPEN-LABEL, MULTICENTER TRIAL OF ARV-471 (PF-07850327) VS FULVESTRANT IN PARTICIPANTS WITH ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE ADVANCED BREAST CANCER WHOSE DISEASE PROGRESSED AFTER PRIOR ENDOCRINE BASED TREATMENT FOR ADVANCED DISEASE (VERITAC-2)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 624
- 试验地点
- 592
- 主要终点
- Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) Assessment Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1- All Randomized Participants
研究概览
简要总结
A study to learn about a new medicine called ARV-471 (PF-07850327) in people who have advanced metastatic breast cancer.
详细描述
The purpose of this study is to learn about the safety and effects of the study medicine ARV-471 (PF-07850327, vepdegestrant) compared to fulvestrant (FUL) in participants with advanced breast cancer. Advanced breast cancer is difficult to cure or control with treatment. The cancer may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body, i.e. bones, lungs, brain, or liver. FUL is a medicine already used for treatment of breast cancer while ARV-471 is a new medicine.
This study is seeking participants with breast cancer who:
- have cancer that has come back in the place where it started or spread to nearby tissue, lymph nodes, or distant parts of the body.
- cannot be fully cured by surgery or radiation therapy. Radiation therapy is the use of high-energy radiation such as x-rays, gamma rays and other sources to kill cancer cells and shrink tumors.
- respond to hormonal or endocrine therapy (which target hormones and/or activity of hormone receptors) such as tamoxifen or aromatase inhibitors (this is called estrogen receptor positive disease)
- have received one line of CDK4/6 inhibitor therapy (for example palbociclib, ribociclib or abemaciclib) in combination with endocrine therapy (for example letrozole) for advanced cancer.
- are allowed up to one other endocrine therapy (for example exemestane) for advanced cancer.
Half of the participants will be given ARV-471 while the other half of the participants will be given FUL.
Participants who get ARV-471 will take ARV-471 by mouth with food, one time a day. During the first treatment cycle participants who will get FUL will be given FUL by shots into the muscles on Day 1 and again 2 weeks later. After the first month, FUL shots will be given on the first day of each new treatment cycle. One treatment cycle is 28 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Adult participants with loco-regional recurrent or metastatic breast disease not amenable to surgical resection or radiation therapy
- •Confirmed diagnosis of ER+/HER2- breast cancer
- •Prior therapies for locoregional recurrent or metastatic disease must fulfill all the following criteria:
- •One line of CDK4/6 inhibitor therapy in combination with endocrine therapy. Only one line of CDK4/6 inhibitor is allowed in any setting.
- •≤ 1 endocrine therapy in addition to CDK4/6 inhibitor with ET
- •Most recent endocrine treatment duration must have been given for ≥6 months prior to disease progression. This may be the endocrine treatment component of the CDK4/6 inhibitor line of therapy.
- •Radiological progression during or after the last line of therapy.
- •Measurable disease evaluable per Response Evaluation Criterion in Solid Tumors (RECIST) v.1.1 or non-measurable bone-only disease
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Participants should be willing to provide blood and tumor tissue
排除标准
- •Participants with advanced, symptomatic visceral spread, that are at risk of life-threatening complications in the short term
- •Prior treatment with:
- •ARV-471, fulvestrant, elacestrant, mTOR, PI3K, AKT pathway inhibitors, PARP inhibitor for any setting
- •other investigational agents (including novel endocrine therapy any SERDs, SERCAs, CERANs) for any setting
- •prior chemotherapy for advanced/metastatic disease
- •Inadequate liver, kidney and bone marrow function
- •Active brain metastases
- •Participants with significant concomitant illness
研究组 & 干预措施
ARV-471
干预措施: ARV-471 (Drug)
Fulvestrant
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) Assessment Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1- All Randomized Participants
时间窗: From date of randomization to date of first documentation of objective PD or death (any cause) or censoring date, whichever occurred first (up to 18.56 months and 19.38 months of treatment exposure for vepdegestrant and fulvestrant arms respectively)
PFS assessed by BICR was defined as the time from the date of randomization to the date of the first documentation of objective progression of disease (PD) per RECIST v1.1, or death due to any cause, whichever occurred first. PD as per RECIST v1.1 was defined as at least a 20% increase in the sum of diameters of target measurable lesions above nadir (smallest sum observed considering baseline and all assessments prior to the timepoint under evaluation), with a minimum absolute increase of 5 millimeters (mm) relative to nadir or unequivocal progression of existing non-target lesions or the presence of new lesions. PFS was censored on the date of last adequate disease assessment for those who did not have a PFS event, discontinued the study treatment due to withdrawal of consent prior to an event, started a new anticancer therapy prior to an event, had an event after a gap of 2 or more missing disease assessments, or lost to follow-up. Kaplan-Meier method was used.
PFS by BICR Assessment Per RECIST v1.1-Participants With ESR1 Mutation
时间窗: From date of randomization to date of first documentation of objective PD or death (any cause) or censoring date, whichever occurred first (up to 18.56 months and 19.38 months of treatment exposure for vepdegestrant and fulvestrant arms respectively)
PFS assessed by BICR was defined as the time from the date of randomization to the date of the first documentation of objective PD per RECIST v1.1, or death due to any cause, whichever occurred first. PD as per RECIST v1.1 was defined as at least a 20% increase in the sum of diameters of target measurable lesions above nadir (smallest sum observed considering baseline and all assessments prior to the timepoint under evaluation), with a minimum absolute increase of 5 mm relative to nadir or unequivocal progression of existing non-target lesions or the presence of new lesions. PFS was censored on the date of last adequate disease assessment for those who did not have a PFS event, discontinued the study treatment due to withdrawal of consent prior to an event, started a new anticancer therapy prior to an event, had an event after a gap of 2 or more missing disease assessments, or lost to follow-up. Kaplan-Meier method was used.
次要结局
- Overall Survival (OS)-All Randomized Participants(From date of randomization to the date of death due to any cause or censoring date)
- OS-Participants With ESR1 Mutation(From date of randomization to the date of death due to any cause or censoring date)
- Percentage of Participants With Objective Response (OR) by BICR Assessment- Participants With Measurable Disease at Baseline(From randomization until PD, death or start of new anticancer therapy, whichever occurred first (up to 18.56 months and 19.38 months of treatment exposure for vepdegestrant and fulvestrant arms respectively))
- Clinical Benefit Rate (CBR) by BICR Assessment(From randomization until PD, death due to any cause or start of new anticancer therapy, whichever occurred first (up to 18.56 months and 19.38 months of treatment exposure for vepdegestrant and fulvestrant arms respectively))
- Duration of Response (DOR) by BICR Assessment(From first documentation of objective tumor response until confirmed PD or death, whichever occurred first (up to 18.56 months and 19.38 months of treatment exposure for vepdegestrant and fulvestrant arms respectively))
- Number of Participants With Grade Shift From Baseline to Maximum Post-Baseline in Hematology Parameters Assessed by NCI CTCAE v5.0(From baseline up to 28 days after last dose of study treatment (up to 19.56 months and 20.38 months for vepdegestrant and fulvestrant arms respectively))
- Number of Participants With Grade Shift From Baseline to Maximum Post-Baseline in Serum Chemistry Laboratory Abnormalities Assessed by NCI CTCAE v5.0(From baseline up to 28 days after last dose of study treatment (up to 19.56 months and 20.38 months for vepdegestrant and fulvestrant arms respectively))
- Number of Participants According to Categorization of Electrocardiogram (ECG) Parameters(From baseline up to 28 days after last dose of study treatment (up to 19.56 months and 20.38 months for vepdegestrant and fulvestrant arms respectively))
- Number of Participants According to Categorization of QT Interval Corrected Using Fridericia's Formula (QTcF) Results-QTc Substudy Analysis Set(Baseline and from the first dose of study treatment up to the end of treatment (EOT) i.e., 28 days after last dose of study treatment (approximately up to 19.56 months))
- Change From Baseline in European Organization for the Research and Treatment of Cancer and Quality of Life Questionnaire (EORTC QLQ-C30) Score(From baseline up to 28 days after last dose of study treatment)
- Change From Baseline in European Organization for the Research and Treatment of Cancer and Quality of Life Questionnaire-Breast Cancer Specific (EORTC QLQ-BR23) Score(From baseline up to 28 days after last dose of study treatment)
- Change From Baseline in EuroQol 5 Dimensions 5 Level (EQ-5D-5L) Index and Visual Analogue Scale (VAS) Scores(From baseline up to 28 days after last dose of study treatment)
- Change From Baseline in Pain Severity and Pain Interference as Assessed by Brief Pain Inventory Short Form (BPI-SF) Score(From baseline up to 28 days after last dose of study treatment)
- Plasma Concentration of ARV-471 and Its Epimer ARV-473(Anytime between -4 to 0 hours on Day 1 of Cycle 2, Cycle 3, Cycle 5 and Cycle 7 and anytime between 5 to 7 hours on Day 1 of Cycle 2 and Cycle 3)
- Change in Plasma Circulating Tumor DNA (ctDNA) From Baseline(Baseline and up to EOT)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), Treatment Related TEAEs, Grade 3 or 4 and Grade 5 TEAEs as Assessed by NCI CTCAE v5.0(From the first dose of study treatment up to 28 days after last dose of study treatment)