An Interventional, Open-Label, Randomized, Multicenter, Phase 3 Study of PF-07248144 Plus Fulvestrant Compared to Investigator's Choice of Therapy in Adult Participants With Hormone Receptor-Positive, HER2-Negative Advanced/Metastatic Breast Cancer Whose Disease Progressed After Prior CDK4/6 Inhibitor-based Therapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- Pfizer
- 入组人数
- 400
- 试验地点
- 324
- 主要终点
- Progression Free Survival (PFS) as determined by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
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 PF-07248144 when given along with fulvestrant for the possible treatment of HR-positive, HER2-negative advanced or metastatic breast cancer.
HR-positive breast cancer cells have proteins on their surface called receptors that bind to hormones like estrogen and progesterone (female sex hormones). These hormones can promote the growth of cancer cells.
HER2-negative describes cells that have a small amount or none of a protein called HER2 on their surface. In normal cells, HER2 helps control cell growth. Cancer cells that are HER2-negative may grow more slowly and are less likely to recur (come back) or spread to other parts of the body than cancer cells that have a large amount of HER2 on their surface.
Advanced cancer is a term that is often used to describe cancer that is unlikely to be cured.
Metastatic cancer is the type where the cancer cells spread from one part of the body to another.
This study is seeking for participants whose breast cancer has gotten worsen after receiving cyclin dependent kinase (CDK) 4/6 inhibitor-based therapy.
Half of participants in this study will receive their usual study treatment, everolimus with endocrine therapy (either exemestane or fulvestrant) for HR-positive/HER2-negative advanced or metastatic breast cancer (A/mBC). The study doctor will discuss which hormone therapy is right for the participant before treatment begins.
PF-07248144 is a tablet that will be taken by mouth at home every day in a 28-day cycle. Fulvestrant will be given as two injections (one injection in the buttock) at visits to the study clinic. Everolimus and exemestane are also tablets and will be taken by mouth at home every day in a 28-day cycle.
The study will compare the experiences of people receiving PF-07248144 in combination with fulvestrant to those of the people who do not. This will help see if PF-07248144 in combination with fulvestrant is safe and effective.
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
- •Confirmed diagnosis of HR-positive HER2-negative breast cancer with evidence of locally advanced or metastatic disease, which is not amenable to surgical resection or radiation therapy with curative intent.
- •Prior CDK4/6 inhibitor therapy in combination with endocrine therapy in advance metastatic setting or in adjuvant setting with documented progression during or within 12 months after the last dose of CDK4/6i.
- •Participants are eligible if they previously received CDK4/6i or ET as a monotherapy, or in combination for rechallenge therapy in the advance or metastatic setting; have received prior therapy targeting estrogen receptor 1 (ESR1) or breast cancer gene (BRCA)1/
- •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 (PS) 0 or 1.
排除标准
- •Documented detectable PIK3CA/AKT1/PTEN alterations in tissue
- •Received greater than two prior lines of systemic therapy in the advance or metastatic setting
- •Had received any prior chemotherapy, including antibody drug conjugates (ADCs), in advance or metastatic setting. Participants who have previously received chemotherapy in the (neo)adjuvant setting are not excluded from the study.
- •Any medical or psychiatric condition that may increase the risk of study participation or make the participant inappropriate for the study.
- •Renal impairment, hepatic dysfunction, or hematologic abnormalities.
研究组 & 干预措施
Arm A: PF-07248144 plus fulvestrant
PF-07248144 tablet taken by mouth plus fulvestrant taken as a shot into the muscle.
干预措施: PF-07248144 (Drug)
Arm A: PF-07248144 plus fulvestrant
PF-07248144 tablet taken by mouth plus fulvestrant taken as a shot into the muscle.
干预措施: Fulvestrant (Drug)
Arm B: everolimus plus ET
Everolimus tablet taken by mouth plus investigator's choice of endocrine therapy of exemestane tablet taken by mouth or fulvestrant taken as a shot into the muscle.
干预措施: Fulvestrant (Drug)
Arm B: everolimus plus ET
Everolimus tablet taken by mouth plus investigator's choice of endocrine therapy of exemestane tablet taken by mouth or fulvestrant taken as a shot into the muscle.
干预措施: Everolimus (Drug)
Arm B: everolimus plus ET
Everolimus tablet taken by mouth plus investigator's choice of endocrine therapy of exemestane tablet taken by mouth or fulvestrant taken as a shot into the muscle.
干预措施: Exemestane (Drug)
结局指标
主要结局
Progression Free Survival (PFS) as determined by blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
时间窗: From the date of randomization until disease progression or death due to any cause (up to approximately 2 years)
次要结局
- Number or Patients with AEs by Incidence(From screening until 28 days after the last dose, to approximately 5 years)
- Number or Patients with AEs by Seriousness(From screening until 28 days after the last dose, to approximately 5 years)
- Number or Patients with AEs by relationship to study interventions(From screening until 28 days after the last dose, to approximately 5 years)
- Number of Participants With Abnormal Electrocardiogram (ECG; Arm A and B)(From screening until 28 days after the last dose, to approximately 5 years)
- Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval (Arm A only)(0h pre-dose on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, and Cycle 3 Day 1; additional 4 hrs post dose on Cycle 1 Day 15 and Cycle 2 Day 1)
- Number of Participants With Laboratory Test Abnormalities(From screening until 28 days after the last dose, to approximately 5 years)
- Overall Survival (OS)(From the date of randomization until death due to any cause (up to approximately 5 years).)
- Number of Participants with Objective Response (OR) by BICR(From the date of randomization until disease progression or death due to any cause (up to approximately 2 years))
- Duration of Response (DoR) as defined by BICR(From the date of the first objective (PR or CR) response (every 8 weeks during the first 48 weeks and then every 12 week) up to approximately 2 years.)
- Number of Participants With Clinical Benefit Response (CBR) by BICR(From randomization date (every 8 weeks during the first 48 weeks and then every 12 weeks) up to approximately 2 years.)
- Number or Patients with Adverse Events (AEs) by Type(From screening until 28 days after the last dose, to approximately 5 years)
- Number or Patients with AEs by Incidence(From screening until 28 days after the last dose, to approximately 5 years)
- Number or Patients with AEs by Seriousness(From screening until 28 days after the last dose, to approximately 5 years)
- Number or Patients with AEs by relationship to study interventions(From screening until 28 days after the last dose, to approximately 5 years)
- Number of Participants With Abnormal Electrocardiogram (ECG; Arm A and B)(From screening until 28 days after the last dose, to approximately 5 years)
- Number of Participants With Increase From Baseline in Corrected QT (QTc) Interval (Arm A only)(0h pre-dose on Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1, and Cycle 3 Day 1; additional 4 hrs post dose on Cycle 1 Day 15 and Cycle 2 Day 1)
- Number of Participants With Laboratory Test Abnormalities(From screening until 28 days after the last dose, to approximately 5 years)
- Ctrough of PF-07248144(Cycle 1 (Day 1), Cycle 1 (Day 15), Cycle 2 (Day 1), and Cycles 3, 5, and 7 (Day 1) only. Each Cycle is 28 days)