A Phase 1/2 Trial of Adagrasib in Combination With Nab-Sirolimus in Patients With Advanced Solid Tumors and Non-Small Cell Lung Cancer With a KRAS G12C Mutation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 3
- 主要终点
- Phase 1: Safety and tolerability in the study population.
研究概览
简要总结
This study will evaluate the safety, MTD and/or RP2D, PK, and clinical activity of the combination of adagrasib with nab-sirolimus in patients with advanced solid tumors/NSCLC with a KRAS G12C mutation.
详细描述
This study will evaluate the safety and tolerability and clinical activity of adagrasib in combination with nab-sirolimus in patients with advanced solid tumors harboring a KRAS G12C mutation.
The Phase 1 portion will enroll advanced solid tumors to establish the maximum tolerated dose (MTD) and/or to identify recommended Phase 2 combinatorial doses. The Phase 2 portion will enroll patients with NSCLC to further evaluate the safety/tolerability and clinical activity.
Adagrasib is an orally available small molecule inhibitor of KRAS G12C. nab-Sirolimus is a nanoparticle albumin-bound (nab) form of sirolimus, and sirolimus is an inhibitor of mechanistic target of rapamycin kinase (mTOR, previously known as mammalian target of rapamycin).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 confirmed diagnosis of solid tumor malignancy (Phase 1) or NSCLC (Phase 2) with KRAS G12C mutation
- •Unresectable or metastatic disease
- •No available treatment with curative intent
- •Adequate organ function
- •Measurable disease per RECIST 1.1.
排除标准
- •History of intestinal disease, inflammatory bowel disease, major gastric surgery, or other gastrointestinal conditions likely to alter absorption of study treatment or result in inability to swallow
- •History of interstitial lung disease or radiation pneumonitis requiring steroid treatment, or any evidence of clinically active interstitial lung disease or pneumonitis
- •Cardiac abnormalities
研究组 & 干预措施
Dose Escalation and Clinical Efficacy
Dose escalation of adagrasib and nab-Sirolimus to determine maximum tolerated dose in combination and evaluate the clinical efficacy of adagrasib in combination with nab-sirolimus in patients with solid tumors (Phase 1) and NSCLC (Phase 2) harboring a KRAS G12C mutation
干预措施: Adagrasib (Drug)
Dose Escalation and Clinical Efficacy
Dose escalation of adagrasib and nab-Sirolimus to determine maximum tolerated dose in combination and evaluate the clinical efficacy of adagrasib in combination with nab-sirolimus in patients with solid tumors (Phase 1) and NSCLC (Phase 2) harboring a KRAS G12C mutation
干预措施: nab-Sirolimus (Drug)
结局指标
主要结局
Phase 1: Safety and tolerability in the study population.
时间窗: 30 months
Safety characterized by the following, as noted from first dose of study treatment to 28 days after last dose of study treatment: 1. Type, incidence, severity, timing, seriousness and relationship to study treatment of Adverse Events 2. Laboratory abnormalities, as measured by changes in lab results such as hematologic or chemistry parameters while on study treatment 3. Number of patients modifying or discontinuing study treatment due to an AE
Phase 1: Maximum tolerated dose (MTD) and Recommended Phase 2 Dose (RP2D)
时间窗: 30 months
Evaluate safety and assess number of patients with dose-limiting toxicity to determine the MTD/RP2D.
Phase 2: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) (Phase 2)
时间窗: 30 months
ORR evaluation of subjects treated with adagrasib in combination with nab-sirolimus in patients with NSCLC with KRAS G12C mutation (Study Population) will be completed. Objective response is the proportion of subjects that experience confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 during the time period from first dose of study treatment until last dose of study treatment.
次要结局
- Area under the plasma concentration versus time curve (AUC)(Up to 7 days)
- Maximum observed plasma concentration(Up to 1 days)
- Phase 1: Objective Response Rate (ORR) using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)(30 months)
- Phase 2: Safety and tolerability in the study population.(30 months)
- Time to achieve maximal plasma concentration(Up to 1 days)
- Terminal elimination half-life(Up to 7 days)
- Phase 1 and 2: Evaluate efficacy endpoints characterized by overall survival, progression-free survival, and duration of response in the study population.(30 months)