NCT06040541招募中1 期
Phase 1/1b, Multicenter, Open-Label, Study of RMC 9805 in Participants With Advanced KRASG 12D-Mutant Solid Tumors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 604
- 试验地点
- 34
- 主要终点
- Adverse events
研究概览
简要总结
This study is to evaluate the safety and tolerability of RMC-9805 as monotherapy and in combination with RMC-6236 in adults with KRAS G12D-mutant solid tumors.
详细描述
This is an open-label, multicenter, Phase 1/1b study of RMC-9805, a selective and orally bioavailable KRAS G12D(ON) inhibitor, in subjects with KRASG12D-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of two arms: RMC-9805 monotherapy arm and RMC-9805 plus RMC-6236 combination arm. Both arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Pathologically documented, locally advanced or metastatic solid tumor with a KRAS G12D-mutation
- •Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage
- •ECOG performance status 0 or 1
- •Adequate organ function
排除标准
- •Primary central nervous system (CNS) tumors
- •Known or suspected leptomeningeal or active brain metastases or spinal cord compression
- •Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication
- •Participant was previously treated with an investigational KRAS G12D inhibitor, pan- or multi-RAS inhibitor, or had prior therapy with any direct RAS-targeted therapy (eg, degraders and inhibitors)
- •Other inclusion/exclusion criteria may apply.
研究组 & 干预措施
RMC-9805 plus RMC-6236 combination arm
Experimental
Dose exploration and dose expansion
干预措施: RMC-9805 (Drug)
RMC-9805 monotherapy arm
Experimental
Dose exploration and dose expansion
干预措施: RMC-9805 (Drug)
RMC-9805 plus RMC-6236 combination arm
Experimental
Dose exploration and dose expansion
干预措施: RMC-6236 (Drug)
结局指标
主要结局
Adverse events
时间窗: Up to 3 years
Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs, and vital signs
Dose Limiting Toxicities
时间窗: 21 days
Number of participants with Dose Limiting Toxicities (DLTs)
次要结局
- Ratio of accumulation of RMC-9805 from a single dose to steady state with repeated dosing as monotherapy and in combination with RMC-6236, and ratio of accumulation of RMC-6236 in combination with RMC-9805(up to 21 weeks)
- Duration of Response (DOR)(up to 3 years)
- Disease Control Rate (DCR)(up to 3 years)
- Area Under Blood Concentration Time Curve (AUC) of RMC-9805 as monotherapy and in combination with RMC-6236, and AUC of RMC-6236 in combination with RMC-9805(up to 21 weeks)
- Progression-Free Survival (PFS)(up to 3 years)
- Elimination Half-Life (t1/2) of RMC-9805 as monotherapy and in combination with RMC-6236, and t1/2 of RMC-6236 in combination with RMC-9805(up to 21 weeks)
- Time to Response (TTR)(up to 3 years)
- Maximum Observed Blood Concentration (Cmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Cmax of RMC-6236 in combination with RMC-9805(up to 21 weeks)
- Time to Reach Maximum Blood Concentration (Tmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Tmax of RMC-6236 in combination with RMC-9805(up to 21 weeks)
- Overall Response Rate (ORR)(up to 3 years)
研究者
研究点 (34)
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相关资讯
Daraxonrasib and Zoldonrasib Show Promise in RAS-Mutated Pancreatic Cancer• Daraxonrasib demonstrates encouraging antitumor activity and manageable safety in RAS-mutated pancreatic ductal adenocarcinoma (PDAC), showing potential to inhibit major RAS variants.
• Zoldonrasib, a KRAS G12D-selective inhibitor, exhibits preliminary antitumor activity and is well-tolerated in patients with KRAS G12D-mutated PDAC.
• Clinical trials reveal significant reductions in RAS variant allele frequency (VAF) in circulating tumor DNA (ctDNA) with both daraxonrasib and zoldonrasib.
• Ongoing phase 3 trial (RASolute 302) will further evaluate daraxonrasib as a second-line treatment for metastatic PDAC compared to chemotherapy.last yearRMC-9805 Demonstrates Promising Activity in KRAS G12D-Mutated Pancreatic Cancer- RMC-9805, a novel oral RAS(ON) G12D-selective covalent inhibitor, shows encouraging safety and anti-tumor activity in pancreatic cancer patients.
- In a Phase 1/1b trial, RMC-9805 achieved a 30% objective response rate and an 80% disease control rate in previously treated KRAS G12D-mutant PDAC.
- The study indicates that RMC-9805 has the potential as a monotherapy or in combination treatments for pancreatic cancer, addressing a significant unmet need.
- RMC-9805 was generally well-tolerated, with mostly grade 1 or 2 treatment-related adverse events and no dose-limiting toxicities reported.last year