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 AND OLDER WITH ER+ ADVANCED OR METASTATIC BREAST CANCER, SUB-STUDY C (ARV-471 IN COMBINATION WITH SAMURACICLIB)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 11
- 试验地点
- 40
- 主要终点
- Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.
研究概览
简要总结
The purpose of this study is to learn about the safety and effects of the study medicine called vepdegestrant. The safety and effects of vepdegestrant will be see when given with other medicines. 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.
This study is divided into separate sub-studies.
For Sub-Study C:
All the participants will receive vepdegestrant and a medicine called samuraciclib.
Vepdegestrant and samuraciclib will be taken once in a day 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 medicine is safe and effective.
Participant will continue to take vepdegestrant and samuraciclib 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
C4891024 is a prospective, open-label, multicenter, Phase 1b/2 sub-study to evaluate the safety, antitumor activity, and PK of ARV-471 with samuraciclib 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 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 breast cancer. At time of enrollment this must not be amendable 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: up to 2 lines of prior therapies for advanced/metastatic disease; 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 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
- •impaired cardiovascular function or clinically significant cardiovascular diseases
- •concurrent administration of medications, food, or herb supplements that are strong inhibitors/inducers of CYP3A, strong CYP2D6 inhibitors 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 Samuraciclib
ARV-471 administered orally QD continuously and Samuraciclib administered orally QD continuously on 28-day cycles
干预措施: vepdegestrant (Drug)
ARV-471 in combination with Samuraciclib
ARV-471 administered orally QD continuously and Samuraciclib administered orally QD continuously on 28-day cycles
干预措施: Samuraciclib (Drug)
结局指标
主要结局
Drug Drug Interaction: • To evaluate the effect of ARV 471 on PK of samuraciclib.
时间窗: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days))
Single dose AUC0-72 of samuraciclib with and without coadministration of ARV 471.
Phase 1b: Number of Participants With Dose Limiting Toxicities
时间窗: 28 days
Dose Limiting Toxicities rate for ARV-471 in combination with Samuraciclib, 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.
Drug Drug Interaction: To evaluate the effect of samuraciclib on PK of ARV 471.
时间窗: From the start of Lead-in period (maximum 13 days) to the end of cycle 1 (at least 28 days)
Steady-state Area under the plasma concentration versus time curve (AUCtau) of ARV-471 with and without coadministration of samuraciclib
次要结局
- Phase 2: To evaluate the correlation between TP53 mutation status and antitumor activity(Screening)
- Phase 1b, Drug drug interaction and Phase 2: Evaluation of Safety and Tolerability of ARV-471 in combination with Samuraciclib(First study drug dose through a minimum of 28 Days After Last study drug administration)
- Phase 1b and Phase 2: Plasma concentrations of ARV-471 and samuraciclib.(At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days))
- Phase 2: Overall Survival(Through study completion, up to approximately 3 year)
- Phase 1b: To evaluate antitumor activity of ARV-471 in combination with samuraciclib(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 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 and Phase 2: Progression Free Survival by investigator assessment.(Up to approximately 1 year)
- Phase 1b: Evaluation of effect of samuraciclib on PK of ARV-471(At predefined intervals throughout the treatment period, up to cycle 7 (each cycle is 28 days))