A Phase 1 Study of the SHP2 Inhibitor BBP-398 (Formerly Known as IACS-15509) in Combination With the KRAS-G12C Inhibitor Sotorasib in Patients With Advanced Solid Tumors and a KRAS-G12C Mutation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 28
- 试验地点
- 25
- 主要终点
- Phase 1b Dose Expansion/Optimization Primary Objective: Overall Response Rate (ORR)
研究概览
简要总结
This is a Phase 1 study of BBP-398, a SHP2 inhibitor, in combination with sotorasib, a KRAS-G12C inhibitor (KRAS-G12Ci), in patients with a KRAS-G12C mutation.
The study involves 2 parts: Phase 1a Dose Escalation and Phase 1b Dose Expansion/Optimization.
详细描述
The primary objectives for Phase 1a Dose Escalation are to evaluate safety and tolerability, and recommend a phase 1b dose (RP1bD) of the combination.
The primary objectives for Phase 1b Dose Expansion/Optimization are to evaluate safety and tolerability, and the antitumor activity (defined by the ORR assessed by the investigator according to RECIST v1.1) of BBP-398 when used in combination with sotorasib across two dose regimens in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS-G12C mutation and who are KRAS-G12Ci naïve, and recommend a phase 2 dose (RP2D) of the combination.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have histologically documented, locally advanced and unresectable, or metastatic solid tumor with documentation of a KRAS-G12C mutation within 2 years prior to screening.
- •Patients must have measurable disease by RECIST v1.
- •Patients must have a minimum life expectancy of >12 weeks after start of study treatment.
- •Patients must have progression or disease recurrence on or after all available standard of care therapies.
- •Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-
- •Patients must have adequate organ function.
排除标准
- •Patients that have participated in an interventional clinical study within the last 4 weeks.
- •Patients that have received radiotherapy or proton therapy with a limited field of radiation for palliation within 1 week of the start of study treatment, OR radiation to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the start of study treatment.
- •Patients with untreated and/or active CNS metastases.
- •Patients that have a history of allogenic bone marrow transplant.
研究组 & 干预措施
Dose Escalation: BBP-398 Level 1 and sotorasib
BBP-398 dose Level 1 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle
干预措施: BBP-398 (Drug)
Dose Escalation: BBP-398 Level 1 and sotorasib
BBP-398 dose Level 1 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle
干预措施: sotorasib (Drug)
Dose Escalation: BBP-398 Level 2 and sotorasib
BBP-398 dose Level 2 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle
干预措施: BBP-398 (Drug)
Dose Escalation: BBP-398 Level 2 and sotorasib
BBP-398 dose Level 2 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle
干预措施: sotorasib (Drug)
Dose Escalation: BBP-398 Level 3 and sotorasib
BBP-398 dose Level 3 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle
干预措施: BBP-398 (Drug)
Dose Escalation: BBP-398 Level 3 and sotorasib
BBP-398 dose Level 3 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle
干预措施: sotorasib (Drug)
Dose Expansion/Optimization: BBP-398 Dose Regimen 1 and sotorasib
BBP-398 Dose Regimen 1 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle
干预措施: BBP-398 (Drug)
Dose Expansion/Optimization: BBP-398 Dose Regimen 1 and sotorasib
BBP-398 Dose Regimen 1 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle
干预措施: sotorasib (Drug)
Dose Expansion/Optimization: BBP-398 Dose Regimen 2 and sotorasib
BBP-398 Dose Regimen 2 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle
干预措施: BBP-398 (Drug)
Dose Expansion/Optimization: BBP-398 Dose Regimen 2 and sotorasib
BBP-398 Dose Regimen 2 capsules administered once a day (QD) for a 28-day treatment cycle in combination with sotorasib tablets administered once a day (QD) for a 28-day treatment cycle
干预措施: sotorasib (Drug)
结局指标
主要结局
Phase 1b Dose Expansion/Optimization Primary Objective: Overall Response Rate (ORR)
时间窗: 8 weeks
Complete Response (CR) + Partial Response (PR) rates, defined by RECIST v1.1
Phase 1b Dose Expansion/Optimization Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, and Serious Adverse Events
时间窗: Completion of 1 Cycle (28 days)
Number of patients experiencing treatment-emergent adverse events, serious adverse events, including changes in lab parameters, vital signs and electrocardiogram changes; duration, and severity based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Phase 1a Dose Escalation Primary Objective: Incidence and Severity of Treatment-Emergent Adverse Events, Serious Adverse Events, and Dose Limiting Toxicities
时间窗: Completion of 1 Cycle (28 days)
Number of patients experiencing treatment-emergent adverse events, serious adverse events, including changes in lab parameters, vital signs and electrocardiogram changes; duration, and severity based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0
次要结局
- Progression Free Survival (PFS)(8 weeks)
- Phase 1a Dose Escalation Secondary Objectives: Overall Response Rate (ORR)(8 weeks)
- Area under the plasma concentration-time curve (AUC) over dosing interval of sotorasib(Cycle 2 Day 1)
- Half-life (T1/2) of sotorasib(Cycle 2 Day 1)
- Observed Maximum Plasma Concentration (Cmax) of sotorasib(Cycle 2 Day 1)
- Overall survival (OS)(8 weeks)
- Half-life (T1/2) of BBP-398(Cycle 2 Day 1)
- Circulating and intratumoral target engagement biomarkers of BBP-398 activity in combination with sotorasib(24 months)
- Duration of response(8 weeks)
- Maximum Observed Plasma Concentration (Cmax) of BBP-398(Cycle 2 Day 1)
- Time to Cmax (Tmax) of BBP-398(Cycle 2 Day 1)
- Area under the plasma concentration-time curve (AUC) of BBP-398(Cycle 2 Day 1)
- Time to Cmax (Tmax) of sotorasib(Cycle 2 Day 1)