A Phase 1 Study of the SHP2 Inhibitor BBP-398 (Formerly Known as IACS-15509) in Combination With the Programmed Death Receptor-1 Blocking Antibody Nivolumab in Patients With Advanced Non-Small Cell Lung Cancer With a KRAS Mutation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 21
- 试验地点
- 15
- 主要终点
- Phase 1a Dose Escalation: Assess safety, tolerability, and recommended phase 2 dose (RP2D) of BBP-398 in combination with nivolumab
研究概览
简要总结
This is a Phase 1 study of BBP-398, a SHP2 inhibitor, in combination with nivolumab, a PD-1 antibody, in patients with NSCLC with a KRAS mutation. The study involves 2 parts: Phase 1a Dose Escalation and Phase 1b Dose Expansion.
详细描述
The primary objective for Phase 1a Dose Escalation is to evaluate the safety, tolerability, and RP2D of BBP-398, a SHP2 inhibitor, when used in combination with nivolumab in patients with advanced NSCLC with a KRAS mutation who have failed standard of care treatment.
The primary objective for Phase 1b Dose Expansion is to evaluate the antitumor activity of BBP-398, as defined by the ORR (per investigator) according to RECIST v1.1, when used in combination with nivolumab in patients with advanced NSCLC with a KRAS mutation who have failed standard of care treatment.
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
- •Patients must have histologically documented, locally advanced and unresectable, or metastatic NSCLC with documentation of a KRAS mutation within the 1 year 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 at least one prior line of systemic therapy, which must include platinum-based doublet chemotherapy and anti-PD-(L)1 therapy.
- •Patients must have experienced progressive or recurrent disease occurring either during treatment or within 90 days after discontinuing anti-PD-(L)1 therapy.
- •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 known central nervous system (CNS) tumors or active CNS metastases.
- •Patients that have experienced progressive disease (PD) within the first 120 days of initiating treatment with an anti- PD-(L)1 agent (e.g., primary refractory).
- •Patients that have a history of allogenic bone marrow transplant.
- •Patients that have select known or suspected autoimmune disease.
- •Patients that have a condition requiring systemic treatment with either corticosteroids (>10 mg prednisone equivalent) or other immunosuppressive medication within 14 days of study start.
- •Patients that have received any live/attenuated vaccine within 30 days of first study treatment.
研究组 & 干预措施
Dose Escalation Level 1
Level 1 oral capsules administered in combination with nivolumab
干预措施: BBP-398 with nivolumab (Drug)
Dose Escalation Level 2
Level 2 oral capsules administered in combination with nivolumab
干预措施: BBP-398 with nivolumab (Drug)
Dose Escalation Level 3
Level 3 oral capsules administered in combination with nivolumab
干预措施: BBP-398 with nivolumab (Drug)
Dose Expansion
RP2D defined dose. Oral capsules administered in combination with nivolumab
干预措施: BBP-398 with nivolumab (Drug)
结局指标
主要结局
Phase 1a Dose Escalation: Assess safety, tolerability, and recommended phase 2 dose (RP2D) of BBP-398 in combination with nivolumab
时间窗: Completion of 1 Cycle (28 days)
Phase 1b Dose Expansion: Assess antitumor activity of BBP-398 in combination with nivolumab
时间窗: Completion of 1 Cycle (28 days)
Anti-tumor activity will be defined by objective response rate (ORR) according to RECIST v1.1
次要结局
- Assess preliminary antitumor activity of BBP-398 in combination with nivolumab(Completion of 1 Cycle (28 days))
- Phase 1b Dose Expansion: Assess safety and tolerability of BBP-398 at the RP2D, in combination with nivolumab(Completion of 1 Cycle (28 days))