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 A (ARV-471 IN COMBINATION WITH ABEMACICLIB)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 37
- 试验地点
- 62
- 主要终点
- Phase 2: percentage of participants with objective response by investigator assessment
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 A:
All participants will receive ARV-471 and a medicine called abemaciclib. ARV-471 will be given by mouth, at home, 1 time a day. Abemaciclib will be given by mouth, at home, 2 times a day. We will examine the experiences of people receiving the study medicines. This will help us determine if the study medicines are safe and effective.
Participants will continue to take ARV-471 and abemaciclib 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
C4891006 is a sub-study from the Umbrella platform, TACTIVE-U, comprising multiple sub-studies that independently evaluate ARV-471 in participants with Estrogen Receptor Positive (ER+) Advanced or Metastatic Breast Cancer (A/MBC). 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 line of any CDK4/6 inhibitor-based regimen is required (independent of the setting eg, adjuvant or advanced/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 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 Abemaciclib
ARV-471 administered orally once daily (QD) and Abemaciclib orally twice daily (BID) on 28-day cycle
干预措施: ARV-471 (Drug)
ARV-471 in combination with Abemaciclib
ARV-471 administered orally once daily (QD) and Abemaciclib orally twice daily (BID) on 28-day cycle
干预措施: Abemaciclib (Drug)
结局指标
主要结局
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.
Phase 1b: number of participants with dose limiting toxicities
时间窗: 28 days
Dose Limiting Toxicities rate for ARV-471 in combination with abemaciclib, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1 \[28 days\]).
次要结局
- Phase 1b 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: number of participants with lab abnormalities - Hematology and coagulation parameters(Up to 28 days after last dose of study treatment)
- Phase 1b: percentage of participants with objective response by investigator assessment(Up to approximately 1 year)
- Phase 1b and Phase 2: number of participants with lab abnormalities - chemistry parameters(Up to 28 days after last dose of study treatment)
- Phase 1b and Phase 2: duration of response by investigator assessment.(Up to approximately 3 years)
- Phase 1b: Maximum Observed Plasma Concentration (Cmax) of abemaciclib with or without ARV-471(Phase 1b: pre-dose Day -1, 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 29 and 43)
- Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.(Up to approximately 1 year)
- Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of abemaciclib(Phase 1b: pre-dose Day -1, 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 29, 43 and 57 Phase 2: pre and post dose Day 15, 29 and 43; pre - dose Day 57, 113 and 169)
- Phase 1b and Phase 2: Progression Free Survival by investigator assessment.(Up to approximately 3 years)
- Phase 2: Overall Survival(Through study completion, up to approximately 3 year)
- Phase 1b: Area Under the Curve from Time Zero to end of dosing interval Evaluation of abemaciclib with or without ARV-471(Phase 1b: pre-dose Day -1, 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day -1 and 15; post dose Day 29 and 43)
- Phase 2:ctDNA plasma quantitative changes from pre-treatment(Day 1, 29 and 57 and End of Treatment (an average of 1 year))
- Phase 1b and Phase 2: Maximum Observed Plasma Concentration (Cmax) of ARV-471(Phase 1b: pre-dose Day 1, 15, 29, 43, 57, 113, 169; 1, 2, 4, 6, 8 hours post dose on Day 15; post dose Day 29 and 43. Phase 2: pre and post dose Day 15, 29 and 43; pre - dose Day 57, 113 and 169)
- Phase 1b and Phase 2: number of participants with lab abnormalities - Hematology and coagulation parameters(Up to 28 days after last dose of study treatment)