A PHASE 3, RANDOMIZED, OPEN-LABEL, MULTICENTER STUDY OF VEPDEGESTRANT (ARV-471/PF-07850327) PLUS PALBOCICLIB VERSUS LETROZOLE PLUS PALBOCICLIB FOR THE TREATMENT OF PARTICIPANTS WITH ESTROGEN RECEPTOR POSITIVE, HER2 NEGATIVE BREAST CANCER WHO HAVE NOT RECEIVED ANY PRIOR SYSTEMIC ANTI CANCER TREATMENT FOR ADVANCED DISEASE (VERITAC-3)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- Pfizer
- 入组人数
- 59
- 试验地点
- 29
- 主要终点
- Study Lead-in (SLI): Incidence of Grade 4 neutropenia
研究概览
简要总结
The purpose of this study is to understand the safety and effects of the study medicine vepdegestrant (ARV-471/PF-07850327) given together with palbociclib in advanced breast cancer. In particular, the study will compare the combination of vepdegestrant plus palbociclib to standard of care therapy (letrozole plus palbociclib). Both letrozole and palbociclib are medicines already used for treatment of breast cancer. Vepdegestrant is a new medicine under study.
This study is seeking participants who have breast cancer that:
- Have a locally advanced or metastatic disease and cannot be fully cured by surgery or radiation therapy. A metastatic disease is when disease has spread to other parts of the body.
- Is sensitive to hormonal therapy such as tamoxifen. This is called estrogen receptor positive disease.
- Have not received any prior medicine for advanced disease. Example medications include tamoxifen or letrozole or exemestane.
The study will have an open-label SLI (study lead-in) before initiation of Phase 3 trial. During SLI, two dose levels of palbociclib in combination with vepdegestrant will be explored in parallel. Assignment to the palbociclib dose is by chance. Half of the participant will receive one dose and the other half another palbociclib dose. The purpose of SLI is to determine the recommended Phase 3 dose of palbociclib to be administered in combination with vepdegestrant.
In the Phase 3, half of the participants will take vepdegestrant plus palbociclib while the other half will take letrozole plus palbociclib. In both SLI and Phase 3, participants will take the study medicines by mouth, with food, once a day. Participants will take the study medicines until breast cancer increase in size or side effects become too severe. Side effects refer to unwanted reactions to medications. Participants will visit the study clinic about once every 4 weeks.
详细描述
The purpose of this study is to demonstrate that vepdegestrant (ARV-471) in combination with palbociclib provides superior clinical benefit compared to letrozole in combination with palbociclib in participants with ER(+)/HER2(-) aBC who have not received any prior systemic anti-cancer therapies for their locoregionally advanced or metastatic disease.
The study will have a Study Lead-in (SLI) and a Phase 3. In the SLI, 50 participants (approximately 25 each arm) will be randomly assigned on a 1:1 basis to one of the two dose levels (DLs). In the randomized Phase 3, approximately 1130 eligible participants (approximately 565 each arm) will be randomized in a 1:1 ratio to the Experimental Arm (ie, vepdegestrant plus palbociclib at RP3D determined in the SLI) or Control Arm (ie, letrozole plus palbociclib at the registered doses). Randomization will be stratified by menopausal status at study entry, visceral disease and de novo metastatic disease.
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 disease not amenable to curative treatment
- •Confirmed diagnosis of ER+/HER2- breast cancer
- •No prior systemic treatment for loco-regional recurrent or metastatic disease
- •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 0-2
- •Phase 3 only: Participants should be willing to provide blood and tumor tissue
排除标准
- •Disease recurrence while on, or within 12 months of completion of adjuvant endocrine therapy
- •Prior treatment with cyclin dependent kinase 4/6 inhibitors (CDK4/6i), vepdegestrant, fulvestrant, elacestrant and other investigational drugs including novel endocrine therapies, any selective estrogen receptor degraders (SERDs), covalent antagonists (SERCAs) and complete ER antagonists (CERANs).
- •Inadequate liver, kidney and bone marrow function
- •Impaired cardiovascular function or clinically significant cardiovascular diseases
- •Refractory nausea and vomiting, inability to swallow capsules and tablets whole, chronic gastrointestinal diseases, significant gastric (total or partial) or bowel resection that would preclude adequate absorption of study interventions.
- •Current use or anticipated need for food, herbal supplements or drugs that are known strong CYP3A4 inhibitors or inducers.
研究组 & 干预措施
Arm A (Investigational Arm)
Participants will receive:
- Vepdegestrant, orally, once daily, continuously, in a 28-day cycle, plus
- Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment in a 28 day cycle
干预措施: Palbociclib (Combination Product)
Arm B (Comparator Arm):
Participants will receive:
- Letrozole, orally, once daily, continuously, in a 28-day cycle, plus
- Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment, in a 28-day cycle.
干预措施: Letrozole (Drug)
Arm B (Comparator Arm):
Participants will receive:
- Letrozole, orally, once daily, continuously, in a 28-day cycle, plus
- Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment, in a 28-day cycle.
干预措施: Palbociclib (Combination Product)
Arm A (Investigational Arm)
Participants will receive:
- Vepdegestrant, orally, once daily, continuously, in a 28-day cycle, plus
- Palbociclib, orally, once daily for 21 consecutive days followed by 7 days off treatment in a 28 day cycle
干预措施: Vepdegestrant (ARV-471/PF-07850327) (Drug)
结局指标
主要结局
Study Lead-in (SLI): Incidence of Grade 4 neutropenia
时间窗: From randomization date up to Cycle 4 (each cycle is 28 days).
It is defined as the number of participants with Grade 4 neutropenia AE (graded by NCI CTCAE v.5.0) with onset within the first 4 cycles divided by the number of participants.
Phase 3: Progression-Free Survival
时间窗: From randomization date, every 12 weeks, to date of first documentation of progression or death, up to approximately 4 years.
Progression-free survival is defined as the time interval from the date of randomization to the date of first documented tumor progression determined by Blinded Independent Central Review (BICR) as per Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) or death due to any cause, whichever come first.
SLI: Incidence of dose reduction
时间窗: From randomization date up to Cycle 4 (each cycle is 28 days).
It is defined as the number of participants reducing the dose of palbociclib and/or vepdegestrant due to any cause occurring within the first 4 cycles divided by the number of participants.
SLI: Incidence of drug discontinuation.
时间窗: From randomization date up to Cycle 4 (each cycle is 28 days).
It is defined as the number of participants discontinuing palbociclib and/or vepdegestrant due to any cause occurring within the first 4 cycles divided by the number of participants.
次要结局
- SLI and Phase 3. Objective Response Rate(From randomization date, every 12 weeks, to the date of progression or death (up to approximately 4 years).)
- SLI and Phase 3: Duration of Response(From the date of the first objective response, every 12 weeks, to the date of disease progression or death (up to approximately 4 years).)
- SLI and Phase 3: Incidence of laboratory abnormalities(From baseline to end of treatment (up to approximately 4 years))
- Phase 3: Disease-related Quality of Life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) core quality of life questionnaire (QLQ-C30)(From baseline, each cycle up to Cycle 3, then every odd cycle to end of treatment (up to approximately 4 years). Each cycle is 28 days.)
- Phase 3: Disease- and treatment-related Quality of Life will be assessed using the European Organization for Research and Treatment of Cancer (EORTC) breast cancer module (QLQ-BR23) questionnaire.(From baseline, each cycle up to Cycle 3, then every odd cycle to end of treatment (up to approximately 4 years). Each cycle is 28 days.)
- SLI and Phase 3: Clinical Benefit Rate(Every 12 weeks From randomization date, every 12 week, to the date of progression or death (up to approximately 4 years).)
- SLI and Phase 3: Incidence of Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)(From baseline to date to end of treatment (up to approximately 4 years))
- SLI and Phase 3: Incidence of Electrocardiogram (ECG) Abnormalities(From baseline up to the end of treatment (up to approximately 4 years))
- Phase 3: Health state utility and health status will be assessed using the European Quality of Life Group questionnaire with 5 dimensions and 5 levels per dimension (EQ-5D-5L)(From baseline, each cycle up to cycle 3, then every odd cycle to end of treatment (up to approximately 4 years). Each cycle is 28 days)
- Phase 3: Changes from baseline in plasma ctDNA (Circulating Deoxyribonucleic Acid)(From baseline to end of treatment (up to approximately 4 years))
- Phase 3: Overall Survival(From randomization date, every 3 months, to date of death (up to approximately 6 years))
- SLI and Phase 3: Plasma concentrations of vepdegestrant and palbociclib(From randomization date up to Cycle 5 (each cycle is 28 days))