A Phase II, Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Neoadjuvant Treatment With Inavolisib Combinations in Patients With Untreated, Early-stage, PIK3CA-Mutated Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 120
- 试验地点
- 50
- 主要终点
- Percentage of Participants with Adverse Events (AEs)
研究概览
简要总结
This study will evaluate the safety and efficacy of inavolisib combination therapies in participants with untreated, PIK3CA-mutated, Stage II-III, estrogen receptor (ER)-positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer (BC).
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed operable or inoperable invasive Stage II-III BC according to American Joint Committee on Cancer (AJCC) TNM staging classification
- •Candidate for neoadjuvant treatment and considered appropriate for endocrine combination therapy
- •Willingness to undergo breast surgery (mastectomy or breast-conserving surgery) after neoadjuvant treatment (unless inoperable)
- •Documented ER-positive tumor in accordance with current American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines
- •Documented HER2-negative tumor in accordance with current ASCO/CAP guidelines
- •Documented Ki-67 score >=5% as per local assessment
- •Confirmed PIK3CA mutation
排除标准
- •Stage IV (metastatic) BC
- •Inflammatory BC (cT4d)
- •Bilateral invasive BC
- •History of ductal carcinoma in situ or lobular carcinoma in situ if they have received any systemic therapy for treatment or radiation therapy to the ipsilateral breast
- •Previous systemic or local treatment for the primary BC currently under investigation (including excisional biopsy or any other surgery of the primary tumor and/or axillary lymph nodes, and sentinel lymph node biopsy, radiotherapy, cytotoxic, and endocrine treatments)
- •Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes
研究组 & 干预措施
Arm B
Participants will receive a starting regimen of inavolisib and letrozole PO QD from Day 1 to 28 in cycle 1 (each cycle=28 days). Starting on Day 1 of Cycle 2, all participants will receive the triplet regimen inavolisib + ribociclib + letrozole as follows: inavolisib and letrozole PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 2-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and letrozole will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Ribociclib (Drug)
Arm C
Participants will receive a starting regimen of ribociclib PO QD from Day 1 to 21 and letrozole PO QD from Day 1 to 28 in cycle 1 (each cycle=28 days). Starting on Day 1 of Cycle 2, all participants will receive the triplet regimen inavolisib + ribociclib + letrozole as follows: inavolisib and letrozole PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 2-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and letrozole will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Ribociclib (Drug)
Arm D (non-randomized)
Participants will receive inavolisib and letrozole PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 1-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and letrozole will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Letrozole (Drug)
Arm E
Participants will receive inavolisib and giredestrant PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 1-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and giredestrant will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Inavolisib (Drug)
Arm E
Participants will receive inavolisib and giredestrant PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 1-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and giredestrant will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Ribociclib (Drug)
Arm E
Participants will receive inavolisib and giredestrant PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 1-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and giredestrant will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Giredestrant (Drug)
Arm G
Participants will receive a starting regimen of ribociclib PO QD from Day 1 to 21 and giredestrant PO QD from Day 1 to 28 in cycle 1 (each cycle=28 days). Starting on Day 1 of Cycle 2, all participants will receive the triplet regimen inavolisib + ribociclib + giredestrant as follows: inavolisib and giredestrant PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 2-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and giredestrant will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Giredestrant (Drug)
Arm G
Participants will receive a starting regimen of ribociclib PO QD from Day 1 to 21 and giredestrant PO QD from Day 1 to 28 in cycle 1 (each cycle=28 days). Starting on Day 1 of Cycle 2, all participants will receive the triplet regimen inavolisib + ribociclib + giredestrant as follows: inavolisib and giredestrant PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 2-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and giredestrant will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Ribociclib (Drug)
Arm G
Participants will receive a starting regimen of ribociclib PO QD from Day 1 to 21 and giredestrant PO QD from Day 1 to 28 in cycle 1 (each cycle=28 days). Starting on Day 1 of Cycle 2, all participants will receive the triplet regimen inavolisib + ribociclib + giredestrant as follows: inavolisib and giredestrant PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 2-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and giredestrant will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Inavolisib (Drug)
Arm F
Participants will receive a starting regimen of inavolisib and giredestrant PO QD from Day 1 to 28 in cycle 1 (each cycle=28 days). Starting on Day 1 of Cycle 2, all participants will receive the triplet regimen inavolisib + ribociclib + giredestrant as follows: inavolisib and giredestrant PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 2-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and giredestrant will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Ribociclib (Drug)
Arm F
Participants will receive a starting regimen of inavolisib and giredestrant PO QD from Day 1 to 28 in cycle 1 (each cycle=28 days). Starting on Day 1 of Cycle 2, all participants will receive the triplet regimen inavolisib + ribociclib + giredestrant as follows: inavolisib and giredestrant PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 2-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and giredestrant will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Giredestrant (Drug)
Arm F
Participants will receive a starting regimen of inavolisib and giredestrant PO QD from Day 1 to 28 in cycle 1 (each cycle=28 days). Starting on Day 1 of Cycle 2, all participants will receive the triplet regimen inavolisib + ribociclib + giredestrant as follows: inavolisib and giredestrant PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 2-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and giredestrant will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Inavolisib (Drug)
Arm A
Participants will receive inavolisib and letrozole orally (PO) once a day (QD) from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 1-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and letrozole will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Inavolisib (Drug)
Arm B
Participants will receive a starting regimen of inavolisib and letrozole PO QD from Day 1 to 28 in cycle 1 (each cycle=28 days). Starting on Day 1 of Cycle 2, all participants will receive the triplet regimen inavolisib + ribociclib + letrozole as follows: inavolisib and letrozole PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 2-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and letrozole will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Letrozole (Drug)
Arm A
Participants will receive inavolisib and letrozole orally (PO) once a day (QD) from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 1-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and letrozole will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Letrozole (Drug)
Arm A
Participants will receive inavolisib and letrozole orally (PO) once a day (QD) from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 1-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and letrozole will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Ribociclib (Drug)
Arm C
Participants will receive a starting regimen of ribociclib PO QD from Day 1 to 21 and letrozole PO QD from Day 1 to 28 in cycle 1 (each cycle=28 days). Starting on Day 1 of Cycle 2, all participants will receive the triplet regimen inavolisib + ribociclib + letrozole as follows: inavolisib and letrozole PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 2-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and letrozole will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Inavolisib (Drug)
Arm B
Participants will receive a starting regimen of inavolisib and letrozole PO QD from Day 1 to 28 in cycle 1 (each cycle=28 days). Starting on Day 1 of Cycle 2, all participants will receive the triplet regimen inavolisib + ribociclib + letrozole as follows: inavolisib and letrozole PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 2-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and letrozole will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Inavolisib (Drug)
Arm C
Participants will receive a starting regimen of ribociclib PO QD from Day 1 to 21 and letrozole PO QD from Day 1 to 28 in cycle 1 (each cycle=28 days). Starting on Day 1 of Cycle 2, all participants will receive the triplet regimen inavolisib + ribociclib + letrozole as follows: inavolisib and letrozole PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 2-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and letrozole will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Letrozole (Drug)
Arm D (non-randomized)
Participants will receive inavolisib and letrozole PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 1-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and letrozole will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Ribociclib (Drug)
Arm D (non-randomized)
Participants will receive inavolisib and letrozole PO QD from Day 1 to 28 and ribociclib PO QD from Day 1 to 21 in cycles 1-5 (each cycle=28 days). In cycle 6, inavolisib, ribociclib and letrozole will be administered PO QD on days 1-21 (each cycle=21 days).
干预措施: Inavolisib (Drug)
结局指标
主要结局
Percentage of Participants with Adverse Events (AEs)
时间窗: From first dose up to 30 days after last dose (approximately 8 months)
次要结局
- Change From Baseline in Ki-67 Levels by Immunohistochemistry (IHC)(Baseline, Day 22 of Cycle 1 and at Surgery (up to approximately 8 months). One cycle = 28 days)
- Percentage of Participants with Total Pathological Complete Response (pCR)(Up to approximately 8 months)
- Percentage of Participants with Objective Response Rate (ORR), According to Modified Response Evaluation Criteria in Solid Tumors, Version 1.1 (mRECIST v1.1)(Up to approximately 8 months)
- Percentage of Participants Reporting Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire(Up to approximately 8 months)
- Percentage of Participants Reporting Each Response Option at Each Time Point for the Treatment Side-Effect Bother Item (GP5) From the Functional Assessment of Cancer Therapy - General (FACT-G) Questionnaire(Up to approximately 8 months)
- Change from Baseline in Symptomatic Treatment-Related Toxicities as Assessed Through use of the PRO-CTCAE(Baseline, up to approximately 8 months)
- Change from Baseline in Treatment Side-Effect Bother as Assessed Through use of the FACT-G GP5 Item(Baseline, up to approximately 8 months)