A Phase 1/2, Open Label, Dose-escalation, and Dose-expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of D3S-001 Monotherapy or Combination Therapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 442
- 试验地点
- 102
- 主要终点
- Number of Participants With Adverse Events (AEs)
研究概览
简要总结
This is a first-in-human (FIH), multicenter, open-label, dose-escalation, and dose-expansion Phase 1/2 clinical trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of D3S-001 or combination therapy in subjects with advanced KRAS p.G12C mutant solid tumors. D3S-001 will be taken daily by oral administration in 21-day treatment cycles.
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
- •Subject must have a histologically or cytologically confirmed metastatic or locally advanced solid tumor which is progressing.
- •Subject must have documented KRAS p.G12C mutation identified within the last 5 years by a local test on tumor tissue or blood.
- •Subject must have measurable disease per RECIST v1.
- •Subject must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Subject must have adequate organ and marrow function within the screening period.
- •Subject has any prior treatment with other treatments without adequate washout periods as defined in the protocol.
- •Subject has uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, uncontrolled or significant cardiovascular disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirements, substantially increase risk of incurring AEs, or compromise the ability of the subject to give written informed consent.
- •Subject has unresolved treatment-related toxicities from previous anticancer therapy of NCI CTCAE Grade ≥2 (with exception of vitiligo or alopecia).
- •Subject has active gastrointestinal disease or other that could interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy.
- •Concurrent participation in any clinical research study involving treatment with any investigational drug, radiotherapy, or surgery, except for the nontreatment phases of these studies (e.g., follow-up phase).
- •Other protocol inclusion/
排除标准
- 未提供
研究组 & 干预措施
D3S-001 monotherapy
Part 1: Dose Escalation, D3S-001 administered orally.
Part 2 and Part 3a Arm C: Dose Expansion, D3S-001 administered orally in selected cancer type patients.
Part 4a: Dose Optimization, D3S-001 administered orally in selected cancer type patients.
干预措施: D3S-001 (Drug)
D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + pemetrexed)
Part 3a Arm B: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients.
Cisplatin + pemetrexed administered intravenously
or
Carboplatin + pemetrexed administered intravenously
干预措施: Pemetrexed (Drug)
D3S-001 and pembrolizumab
Part 3a Arm A: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients.
Pembrolizumab administered intravenously.
干预措施: Pembrolizumab (Drug)
D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + pemetrexed)
Part 3a Arm B: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients.
Cisplatin + pemetrexed administered intravenously
or
Carboplatin + pemetrexed administered intravenously
干预措施: D3S-001 (Drug)
D3S-001 and Cetuximab
Part 3b: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients.
Cetuximab administered intravenously.
干预措施: D3S-001 (Drug)
D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + pemetrexed)
Part 3a Arm B: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients.
Cisplatin + pemetrexed administered intravenously
or
Carboplatin + pemetrexed administered intravenously
干预措施: Cisplatin (Drug)
D3S-001 and platinum doublet chemotherapy (cisplatin + pemetrexed or carboplatin + pemetrexed)
Part 3a Arm B: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients.
Cisplatin + pemetrexed administered intravenously
or
Carboplatin + pemetrexed administered intravenously
干预措施: Carboplatin (Drug)
D3S-001 and Cetuximab
Part 3b: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients.
Cetuximab administered intravenously.
干预措施: Cetuximab (Drug)
D3S-001 and pembrolizumab
Part 3a Arm A: Dose Expansion, D3S-001 in combination therapy administered orally in selected cancer type patients.
Pembrolizumab administered intravenously.
干预措施: D3S-001 (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs)
时间窗: From first dose until 30 days after the last dose (or specified in the protocol).
Number of Participants With Dose-Limiting Toxicities (DLTs)
时间窗: From Cycle 1 Day 1 through Day 21. Each cycle is 21 days.
次要结局
- D3S-001 half-life (t1/2)(Up to 24 months.)
- D3S-001 area under the concentration-time curve (AUC)(Up to 24 months.)
- Progression-free survival (PFS) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)(Up to 24 months.)
- Disease Control Rate (DCR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)(Up to 24 months.)
- Objective response rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)(Up to 24 months.)
- D3S-001 maximum observed plasma concentration (Cmax)(Up to 24 months.)
- D3S-001 time to maximum plasma concentration (tmax)(Up to 24 months.)
- Duration of Response (DOR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)(Up to 24 months.)