AN INTERVENTIONAL SAFETY AND EFFICACY PHASE 1B/2, OPEN-LABEL STUDY TO INVESTIGATE TOLERABILITY, PK, AND ANTITUMOR ACTIVITY OF VEPDEGESTRANT (ARV-471/PF-07850327), AN ORAL PROTEOLYSIS TARGETING CHIMERA, IN COMBINATION WITH PF-07220060 IN PARTICIPANTS AGED 18 YEARS AND OLDER WITH ER+/HER2- ADVANCED OR METASTATIC BREAST CANCER
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 71
- 试验地点
- 53
- 主要终点
- Phase 1b: Number of Participants With Dose Limiting Toxicities
研究概览
简要总结
The purpose of this study is to learn about the safety and effects of giving vepdegestrant along with PF-07220060. Vepdegestrant is studied to see if it can be a possible treatment for advanced metastatic breast cancer. This type of cancer would have spread from where it started (breast) to other parts of the body and would be tough to treat. The study is seeking for participants who have breast cancer that:
- is hard to treat (advanced) and may have spread to other organs (metastatic).
- is sensitive to hormonal therapy (it is called estrogen receptor positive).
- is no longer responding to treatments taken before starting this study.
All the participants will receive vepdegestrant and PF-07220060. Both medicines will be taken by mouth. The medicines will be taken at home. The experience of people receiving the study medicines will be studied. This will help see if the study medicines are safe and effective. Participants will continue to take vepdegestrant and PF-07220060 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
C4891026 is a prospective, open-label, multicenter, Phase 1b/2 study to evaluate the safety, antitumor activity, and pharmacokinetic (PK) of vepdegestrant in combination with PF-07220060 in the treatment of participants with Estrogen Receptor Positive/Human Epidermal Growth Factor Receptor 2 Negative (ER+/HER2-) Advanced or Metastatic 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 breast cancer. At time of enrollment this must not be amenable to surgical resection with curative intent (≥1% ER+ stained cells as per local practice on the most recent tumor biopsy HER2- tumor by IHC or in-situ hybridization per ASCO/CAP).
- •prior anticancer therapies: Phase 1b: at least 1 line of SOC for A/MBC; Prior fulvestrant allowed; ≤1 prior chemotherapy line (no antibody-drug conjugates permitted) for A/MBC setting allowed. Phase 2: At least one and maximum 2 lines of ET in A/MBC setting and most recent ET-based regimen for >6 months.
- •1, and only 1, prior CDK4/6 inhibitor-based regimen required. Up to 1 prior regimen of cytotoxic chemotherapy (no antibody-drug conjugates permitted) in the A/MBC setting; Prior fulvestrant allowed.
- •Participant with only non-measurable lesion (Phase1b) or at least 1 measurable lesion as defined by RECIST v1.
- •(Phase2) are eligible.
- •ECOG PS = 0 or 1 (Phase1b) ; ≤2 (Phase2)
排除标准
- •visceral crisis at risk of life-threatening complications in the short term.
- •Any condition precluding an adeguate absorption of study interventions.
- •newly diagnosed brain metastases, or symptomatic central nervous system (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 28 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 are excluded
- •impaired cardiovascular function or clinically significant cardiovascular diseases.
- •concurrent administration of medications, food, or herb supplements that are strong inhibitors/inducers of CYP3A or UGT2B7, moderate inducers of CYP34 (Phase1b only) 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
vepdegestrant in combination with PF-07220060
vepdegestrant administered orally once daily (QD) continuously and PF-07220060 administered orally twice daily (BID) continuously on 28-day cycles
干预措施: vepdegestrant (Drug)
vepdegestrant in combination with PF-07220060
vepdegestrant administered orally once daily (QD) continuously and PF-07220060 administered orally twice daily (BID) continuously on 28-day cycles
干预措施: PF-07220060 (Drug)
结局指标
主要结局
Phase 1b: Number of Participants With Dose Limiting Toxicities
时间窗: 28 days
Dose Limiting Toxicities (DLTs) rate for Vepdegestrant in combination with PF-07220060, estimated based on data from DLT-evaluable participants during the DLT observation period (Cycle 1).
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.
次要结局
- Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants experiencing any AE, SAE, treatment-related AE and treatment-related SAE)(First study drug dose through a minimum of 28 Days After Last study drug administration)
- Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - Hematology and coagulation parameters)(First study drug dose through a minimum of 28 Days After Last study drug administration)
- Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - chemistry parameters)(First study drug dose through a minimum of 28 Days After Last study drug administration)
- Phase 1b and Phase 2: Evaluation of Safety of Vepdegestrant in combination with PF-07220060 (number of participants with changes from baseline for ECG parameters)(First study drug dose through a minimum of 28 Days After Last study drug administration)
- Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities- Hematology and coagulation parameters)(First study drug dose through a minimum of 28 Days After Last study drug administration)
- Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants with lab abnormalities - chemistry parameters)(First study drug dose through a minimum of 28 Days After Last study drug administration)
- Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants with changes from baseline for ECG parameters)(First study drug dose through a minimum of 28 Days After Last study drug administration)
- Phase 1b: To evaluate antitumor activity of Vepdegestrant in combination with PF-07220060(Up to approximately 1 year)
- Phase 1b and Phase 2: Duration of Response by investigator assessment.(Up to approximately 1 year)
- Phase 1b and Phase2: Percentage of participants with Clinical Benefit Response by investigator assessment.(Up to approximately 1 year)
- Phase 1b and Phase 2: Progression Free Survival by investigator assessment.(Up to approximately 1 year)
- Phase 1b and Phase 2: Evaluation of Tolerability of Vepdegestrant in combination with PF-07220060 (number of participants experiencing any AE, SAE, treatment-related AE and treatment-related SAE)(First study drug dose through a minimum of 28 Days After Last study drug administration)
- Phase 1b and Phase 2: Plasma concentrations of Vepdegestrant, ARV-473 and PF-07220060 when given in combination.(Phase 1b: Pre-dose Day 8; Pre-, 0.5, 1, 2, 4, 6, 8, 12h post-dose Day 15; Pre- and 4-8h post-dose 29; Pre- and 4-8h post-dose Day 43; Pre-dose Days 57, 113 and 169. Phase 2: Pre- and 4-8h post-dose Days 15, 29 and 43; Pre-dose Days 57, 113 and 169)
- Phase 1b: Evaluation of the PK of Vepdegestrant and PF-07220060 when given in combination(Phase 1b (a cycle is 28 days): Pre-dose on Day 8 of Cycle 1; Pre-dose, 0.5, 1, 2, 4, 6, 8, 12h post-dose on Day 15 of Cycle 1; Pre-dose and 4-8h on Day 1 of Cycle 2; Pre-dose and 4-8h post-dose on Day 15 of Cycle 2; Pre-dose on Day 1 of Cycles 3, 5 and 7)
- Phase 2:ctDNA plasma quantitative changes from pre-treatment(Phase 2 (each cycle is 28 days): Pre-dose on Day 1 of Cycles 1, 2 and 3 and after last treatment administration.)