A Phase Ib/II Multicenter, Open-Label, Randomized Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-4198 Alone and in Combination With Giredestrant in Comparison With Abemaciclib and Giredestrant in Participants With Locally Advanced or Metastatic Estrogen Receptor-Positive, HER2-Negative Breast Cancer Who Have Previously Progressed During or After a CDK4/6 Inhibitor
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 285
- 试验地点
- 64
- 主要终点
- Phase Ib: Incidence and Severity of Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to assess the safety of GDC-4198 alone and in combination with giredestrant and also the efficacy of GDC-4198 + giredestrant versus abemaciclib + giredestrant in participants with locally advanced or metastatic ER+, HER2- breast cancer. The study consists of 2 phases: Phase Ib and Phase II. Phase Ib will evaluate the safety and pharmacokinetics (PK) of GDC-4198 alone and in combination with giredestrant. Phase II stage will compare the activity and safety of GDC-4198 and giredestrant with abemaciclib and giredestrant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •Histologically and/or cytologically confirmed adenocarcinoma of the breast that is locally advanced or metastatic.
- •Previously documented ER+ and HER2- tumor according to American Society of Clinical Oncology (ASCO)/ College of American Pathologists (CAP) or European Society of Medical Oncology (ESMO) guidelines or any national guidelines with criteria conforming to ASCO/CAP or ESMO guidelines.
- •Disease progression during or after treatment with an approved cyclin-dependent kinase 4/6 (CDK4/6) inhibitor and approved endocrine therapy (ET) in the locally advanced or metastatic setting.
- •Measurable or non-measurable evaluable, disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Life expectancy >= 6 months.
排除标准
- •Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term appropriate for treatment with cytotoxic chemotherapy at time of entry into the study, as per national or local treatment guidelines.
- •Have received more than one-line of therapy for locally advanced or metastatic disease.
- •Have received prior chemotherapy for metastatic breast cancer.
- •Treatment with an approved oral ET within 7 days prior to initiation of study drug; treatment with fulvestrant or an approved CDK4/6 inhibitor within 21 days prior to initiation of study drug.
- •Malabsorption condition or other gastrointestinal (GI) conditions/surgeries that the investigator assesses may significantly interfere with enteral absorption
- •History of malignancy within 3 years prior to screening, except for cancer under investigation in this study and malignancies with a negligible risk of metastasis or death.
- •Known allergy or hypersensitivity to any component of the study treatments.
研究组 & 干预措施
Phase II: Arm C
Participants will receive abemaciclib, 150 mg twice daily, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).
干预措施: Abemaciclib (Drug)
Phase Ib: Dose-Finding Stage
Participants will receive GDC-4198 as monotherapy and in combination with giredestrant, 30 milligrams (mg), orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).
干预措施: GDC-4198 (Drug)
Phase II: Arm B
Participants will receive GDC-4198, lower dose, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).
干预措施: GDC-4198 (Drug)
Phase II: Arm C
Participants will receive abemaciclib, 150 mg twice daily, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).
干预措施: Giredestrant (Drug)
Phase Ib: Dose-Finding Stage
Participants will receive GDC-4198 as monotherapy and in combination with giredestrant, 30 milligrams (mg), orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).
干预措施: Giredestrant (Drug)
Phase II: Arm A
Participants will receive GDC-4198, higher dose, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).
干预措施: GDC-4198 (Drug)
Phase II: Arm A
Participants will receive GDC-4198, higher dose, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).
干预措施: Giredestrant (Drug)
Phase II: Arm B
Participants will receive GDC-4198, lower dose, in combination with giredestrant, 30 mg, orally, daily, as per a pre-defined dosing regimen during each cycle until unacceptable toxicity or disease progression and/or loss of clinical benefit. (1 cycle=28 days).
干预措施: Giredestrant (Drug)
结局指标
主要结局
Phase Ib: Incidence and Severity of Adverse Events (AEs)
时间窗: Up to 36 months
Severity of AEs determined according to the CTCAE v5.0 grading scale
Phase Ib: Number of Participants With Dose-Limiting Toxicity (DLTs)
时间窗: From Day 1 to Day 28 of Cycle 1 (1 cycle=28 days)
Phase II: Progression-free Survival (PFS)
时间窗: Up to 36 months
次要结局
- Phase II: Recommended Dose of GDC-4198(Up to 36 months)
- Phase II: ORR(Up to 36 months)
- Phase Ib: Objective Response Rate (ORR)(Up to 36 months)
- Phase Ib: Clinical Benefit Rate (CBR)(Up to 36 months)
- Phase II: Duration of Response (DOR)(Up to 36 months)
- Phase II: CBR(Up to 36 months)
- Phase II: Overall Survival (OS)(Up to 36 months)
- Phase II: OS Rate at 6 Months and 12 Months(Month 6, Month 12)
- Phase II: PFS Rate at 6 Months and 12 Months(Month 6, Month 12)
- Phase II: Incidence and Severity of Adverse Events (AEs)(Up to 36 months)
- Phase II: Plasma Concentration of GDC-4198(Up to 36 months)