A Phase 1a/1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Antitumor Activity of BG-75202, Alone and in Combination With Other Agents in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 86
- 试验地点
- 32
- 主要终点
- Part 1: Number of Participants with Adverse Events (AEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of BG-75202 (KAT6A/B inhibitor) alone and in combination with other therapies in participants with breast cancer and other advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Part 1A: Participants with histologically or cytologically confirmed advanced, metastatic breast cancer and other solid tumors who have exhausted, are intolerant of all available standard of care therapies, and/or without available standard of care therapies.
- •Part 1B and Part 2A: Participants with advanced breast cancer with 1 to 3 prior lines of systemic therapy in the metastatic setting. Prior lines in the advanced/ metastatic setting may not exceed 2 lines of chemotherapy (inclusive of antibody-drug conjugate with cytotoxic payload).
- •Parts 2B and 2C: Participants with advanced breast cancer enrolled in regions where cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are not approved and/or not available as the first-line treatment and who are CDK4/6 inhibitor treatment naïve and did not receive any previous systemic treatment for advanced disease.
- •Participants with breast cancer must have histologically or cytologically confirmed advanced breast cancer at the time of most recent testing, based on American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
- •Female participants with metastatic breast cancer must be postmenopausal or receiving ovarian function suppression treatment.
- •Measurable disease as assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.
- •Stable Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Adequate organ function.
排除标准
- •Prior exposure to KAT6A/B or KAT7 inhibitors/degraders.
- •Patients with active leptomeningeal disease or uncontrolled, untreated brain metastasis.
- •Participants with any malignancy ≤ 3 years before screening for the study except for the specific cancer under investigation in this study and any locally recurring cancer that has been treated curatively which in the opinion of the investigator is unlikely to require intervention during the study.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part 1B: Dose Escalation and Safety Expansion, BG-75202 + Estrogen Receptor Antagonist
Sequential cohorts of increasing dose levels of BG-75202 will be evaluated in combination with an estrogen receptor antagonist.
干预措施: Estrogen Receptor Antagonist (Drug)
Part 1B: Dose Escalation and Safety Expansion, BG-75202 + Estrogen Receptor Antagonist
Sequential cohorts of increasing dose levels of BG-75202 will be evaluated in combination with an estrogen receptor antagonist.
干预措施: BG-75202 (Drug)
Part 2A: Dose Optimization, BG-75202 + Estrogen Receptor Antagonist
Participants will receive BG-75202 in combination with an estrogen receptor antagonist.
干预措施: BG-75202 (Drug)
Part 2B: Safety Run-In, BG-75202 + CDK4 inhibitor + Aromatase Inhibitor
Participants will receive BG-75202 in combination with a cyclin-dependent kinase 4 (CDK4) inhibitor and an aromatase inhibitor.
干预措施: Aromatase Inhibitor (Drug)
Part 2C: Dose Expansion, BG-75202 + CDK4 inhibitor + Aromatase Inhibitor
Participants will receive BG-75202 in combination with a CDK4 inhibitor and an aromatase inhibitor.
干预措施: BG-75202 (Drug)
Part 2C: Dose Expansion, BG-75202 + CDK4 inhibitor + Aromatase Inhibitor
Participants will receive BG-75202 in combination with a CDK4 inhibitor and an aromatase inhibitor.
干预措施: CDK4 Inhibitor (Drug)
Part 2C: Dose Expansion, BG-75202 + CDK4 inhibitor + Aromatase Inhibitor
Participants will receive BG-75202 in combination with a CDK4 inhibitor and an aromatase inhibitor.
干预措施: Aromatase Inhibitor (Drug)
Part 1A: Dose Escalation and Safety Expansion, BG-75202 Monotherapy
Sequential cohorts of increasing dose levels of BG-75202 will be evaluated as monotherapy.
干预措施: BG-75202 (Drug)
Part 2B: Safety Run-In, BG-75202 + CDK4 inhibitor + Aromatase Inhibitor
Participants will receive BG-75202 in combination with a cyclin-dependent kinase 4 (CDK4) inhibitor and an aromatase inhibitor.
干预措施: CDK4 Inhibitor (Drug)
Part 2B: Safety Run-In, BG-75202 + CDK4 inhibitor + Aromatase Inhibitor
Participants will receive BG-75202 in combination with a cyclin-dependent kinase 4 (CDK4) inhibitor and an aromatase inhibitor.
干预措施: BG-75202 (Drug)
Part 2A: Dose Optimization, BG-75202 + Estrogen Receptor Antagonist
Participants will receive BG-75202 in combination with an estrogen receptor antagonist.
干预措施: Estrogen Receptor Antagonist (Drug)
结局指标
主要结局
Part 1: Number of Participants with Adverse Events (AEs)
时间窗: From first dose to 30 days after last dose or initiation of a new anticancer therapy, whichever occurs first, up to approximately 12 months
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including physical examination findings, electrocardiogram results, laboratory values, and AEs meeting protocol-defined dose-limiting toxicity (DLT) criteria.
Part 1: Recommended Dose for Expansion (RDFE)
时间窗: Estimated approximately 1 year
The RDFE is based on the maximum tolerated dose (MTD) or maximum administered dose (MAD) with consideration of the tolerability, pharmacokinetics (PK), pharmacodynamics, antitumor activity, and any other available relevant data.
Part 2: Overall Response Rate (ORR)
时间窗: Up to approximately 2 years
ORR is defined as the percentage of participants with partial or complete response, as assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
次要结局
- Parts 1 and 2: Maximum Observed Plasma Concentration (Cmax) of BG-75202(Up to approximately 4 months)
- Parts 1 and 2: Minimum Observed Plasma Concentration (Ctrough) of BG-75202(Up to approximately 4 months)
- Parts 1 and 2: Area Under the Plasma Concentration-Time Curve (AUC) of BG-75202(Up to approximately 4 months)
- Parts 1 and 2: Terminal Half-Life (t1/2) of BG-75202(Up to approximately 4 months)
- Part 1: ORR(Up to approximately 1 year)
- Part 1: Duration of Response (DOR)(Up to approximately 1 year)
- Part 1: Time to Response (TTR)(Up to approximately 1 year)
- Part 2: DOR(Up to approximately 2 years)
- Part 2: TTR(Up to approximately 2 years)
- Part 2: Disease Control Rate (DCR)(Up to approximately 2 years)
- Part 2: Clinical Benefit Rate (CBR)(Up to approximately 2 years)
- Part 2: Progression-Free Survival (PFS)(Up to approximately 2 years)
- Part 2: Number of Participants with Adverse Events (AEs)(Up to approximately 2 years)
- Part 2: Recommended Phase 2 Dose (RP2D)(Up to approximately 2 years)