TACTIVE-U: AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL UMBRELLA STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF VEPDEGESTRANT (ARV-471/PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH OTHER ANTICANCER TREATMENTS IN PARTICIPANTS AGED 18 YEARS AND OVER WITH ER+ ADVANCED OR METASTATIC BREAST CANCER, SUB-STUDY B (ARV-471 IN COMBINATION WITH RIBOCICLIB)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 20
- 试验地点
- 29
- 主要终点
- Drug Drug Interaction cohort: Maximum Plasma Concentration (Cmax) of ribociclib with and without co-administration of ARV-471
研究概览
简要总结
The purpose of this clinical trial is to learn about the safety and effects of the study medicine (called ARV-471) when given together with other medicines for the potential treatment of advanced or metastatic breast cancer.
This study is seeking participants who have breast cancer that:
- is advanced, may have spread to other organs (metastatic) and cannot be fully treated by surgery or radiation therapy
- is sensitive to hormonal therapy (it is called estrogen receptor positive); and
- is no longer responding to previous treatments
This study is divided into separate sub-studies.
For Sub-Study B:
All participants will receive ARV-471 and a medicine called ribociclib. ARV-471 and ribociclib will be given at the same time by mouth, at home, 1 time a day.
The experiences of people receiving the study medicine will be examined. This will help determine if the study medicine is safe and effective.
Participants will continue to take ARV-471 and ribociclib until their cancer is no longer responding, or side effects become too severe. They will have visits at the study clinic about every 4 weeks.
详细描述
C4891023 is a prospective, open-label, multicenter, Phase 1b/2 sub-study to evaluate the safety, antitumor activity, and PK of ARV-471 with ribociclib in the treatment of participants with A/MBC. The sub-study is part of Umbrella platform, TACTIVE-U, comprising multiple sub-studies that independently evaluate ARV-471 in participants with with Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Advanced or Metastatic Breast Cancer. ARV-471 will act as the backbone therapy given in combination with other anticancer agents thought to have clinical relevance in ER+ breast cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •histological or cytological diagnosis of ER+ and HER2- advanced/metastatic breast cancer that is not amendable to surgical resection with curative intent (≥1% ER+ stained cells on the most recent tumor biopsy).
- •prior anticancer therapies: at least 1 and no more than 2 lines of prior therapies for advanced/metastatic disease; 1, and only 1, line of any CDK4/6 inhibitor-based regimen is required (in any setting eg adjuvant, metastatic)
- •at least 1 measurable lesion as defined by RECIST v1.
- •ECOG PS ≤1.
排除标准
- •visceral crisis at risk of life-threatening complications in the short term
- •known history of drug-induced pneumonitis or other significant symptomatic deterioration of lung functions.
- •newly diagnosed brain metastases, or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease. Participants with a history of CNS metastases or cord compression are eligible if they have been definitively treated, clinically stable and discontinued anti-seizure medications and corticosteroids for at least 14 days prior to enrollment in the of study.
- •history of any other tumor malignancies within the past 3 years, except for the following: (1) adequately treated basal or squamous cell carcinoma of the skin; (2) curatively treated in situ carcinoma of the cervix.
- •inflammatory breast cancer
- •impaired cardiovascular function or clinically significant cardiovascular diseases
- •concurrent administration of medications, food, or herb supplements that are strong inhibitors and strong/moderate inducers of CYP3A and drugs known to predispose to Torsade de Pointes or QT interval prolongation.
- •renal impairment, not adequate liver function and/or bone marrow function
- •known active infection
研究组 & 干预措施
ARV-471 in combination with Ribociclib
ARV-471 administered orally QD continuously and Ribociclib administered orally QD consecutively for 21 days followed by 7 days off treatment on 28-day cycles
干预措施: ARV-471 (Drug)
ARV-471 in combination with Ribociclib
ARV-471 administered orally QD continuously and Ribociclib administered orally QD consecutively for 21 days followed by 7 days off treatment on 28-day cycles
干预措施: Ribociclib (Drug)
结局指标
主要结局
Drug Drug Interaction cohort: Maximum Plasma Concentration (Cmax) of ribociclib with and without co-administration of ARV-471
时间窗: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43
Concentration (Cmax) of ribociclib with and without co-administration of ARV-471
Phase 2: Percentage of Participants With Objective Response by investigator assessment
时间窗: Up to approximately 1 year
Objective response (OR) refers to confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1. as determined by investigator assessment.
Drug Drug Interaction cohort: Area Under the Curve from Time Zero to end of dosing interval Evaluation of ribociclib with and without co-administration of ARV-471
时间窗: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43
Exposure (AUCtau) of ribociclib with and without co-administration of ARV-471
Phase 1b: Number of Participants With Dose Limiting Toxicities
时间窗: Cycle 1 (28 days)
Dose Limiting Toxicities rate for ARV-471 in combination with Ribociclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1 \[28 days\]).
次要结局
- Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants with lab abnormalities - chemistry parameters(Up to 28 days after last dose of study treatment)
- Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants with lab abnormalities - Hematology and coagulation parameters(Up to 28 days after last dose of study treatment)
- Phase 2:ctDNA plasma quantitative changes from pre-treatment(At predefined intervals throughout the treatment period, up to cycle 3 (each cycle is 28 days) and end of treatment)
- Phase 1b: Percentage of Participants With Objective Response by investigator assessment(Up to approximately 1 year)
- Phase 1b and Phase 2: Duration of Response by investigator assessment.(Up to approximately 1 year)
- Phase 1b: Maximum Observed Plasma Concentration (Cmax) of ARV-471 with and without co-administration of ribociclib(Phase 1b: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43)
- Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-473(Phase 1b: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43 Phase 2: pre and post dose Day 8, 15, 29 and 43; pre - dose Day 57, 113 and 169)
- Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.(Up to approximately 1 year)
- Phase 1b Area Under the Curve from Time Zero to end of dosing interval Evaluation of ARV-471 with and without co-administration of ribociclib(Phase 1b: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43)
- Drug Drug Interaction cohort: number of participants with changes from baseline for ECG parameters(Up to 28 days after last dose of study treatment)
- Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-471(Phase 1b: pre-dose Day 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 8, 29 and 43 Phase 2: pre and post dose Day 8, 15, 29 and 43; pre - dose Day 57, 113 and 169)
- Phase 1b, Drug Drug Interaction cohort and Phase 2: number of participants experiencing any AE, SAE, Treatment Related SAE(Up to 28 days after last dose of study treatment)
- Phase 1b and Phase 2: Progression Free Survival by investigator assessment.(Up to approximately 1 year)
- Phase 1b and Phase 2: Phase 1b: Maximum Observed Plasma Concentration (Cmax) of ribociclib(Phase 1b: pre-dose Day -1, 1, 8, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day 15; post dose Day 8, 29 and 43 Phase 2: pre and post dose Day 8, 15, 29 and 43; pre - dose Day 57, 113 and 169)
- Phase 2: Overall Survival(Through study completion, up to approximately 3 year)