NCT06162221

Study of RAS(ON) Inhibitors in Patients With Advanced RAS-mutated NSCLC

A Platform Study of RAS(ON) Inhibitors in Patients With RAS-Mutated Non-Small Cell Lung Cancer (NSCLC)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 616 (estimated)
• Sponsor: Revolution Medicines, Inc. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors as a monotherapy or combined with Standard(s) of Care (SOC) or with each other. The first four subprotocols include the following: Subprotocol A: RMC-6291 +/- RMC-6236 + SOC Subprotocol B: RMC-6236 + SOC Subprotocol C: RMC-9805 +/- RMC-6236 + SOC Subprotocol D: RMC-9805

Detailed description

The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents or as a monotherapy to be evaluated in patients with RAS-mutated solid tumors with a focus on NSCLC. This is an open-label platform Phase 1b/2 study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard of Care (SOC), or as a monotherapy and to define the Recommended Phase 2 Dose and Schedule (RP2DS). Enrollment of patients with KRAS or RAS mutations will be specified in each subprotocol. Subprotocol A is an open-label, multicenter, Phase 1b/2 study of RMC-6291, with or without RMC-6236, in combination with pembrolizumab, with or without chemotherapy, in patients with KRAS G12C-mutated advanced solid tumors. Subprotocol B is an open-label, multicenter, Phase1b/2 study of RMC-6236 in combination with pembrolizumab, with or without chemotherapy, in patients with RAS-mutated non-small cell lung cancer (NSCLC) Subprotocol C is an open-label, multicenter, Phase1b/2 study of RMC-9805 with or without RMC-6236, in combination with other anticancer agents, in patients with RAS G12D-mutated non-small cell lung cancer (NSCLC) Subprotocol D is a Phase 2, Open-label, Multicenter Study of Zoldonrasib (RMC-9805) in Previously Treated Patients with RAS G12D-Mutant Non-Small Cell Lung Cancer (NSCLC) Subprotocols A, B, and C consist of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion. Subprotocol D consists of only one part.

Conditions

• Non-Small Cell Lung Cancer, NSCLC
• KRAS, NRAS, HRAS-mutated NSCLC
• KRAS G12C-mutated Solid Tumors, Lung Cancer
• Lung Cancer Stage IV, Advanced Solid Tumor, Cancer
• RAS G12D-mutated NSCLC

Interventions

Type	Name	Description
DRUG	RMC-6291	Oral tablet
DRUG	RMC-6236	Oral tablet
DRUG	Pembrolizumab	IV Infusion
DRUG	Cisplatin	IV Infusion
DRUG	Carboplatin	IV Infusion
DRUG	Pemetrexed	IV infusion
DRUG	RMC-9805	Oral Tablet

Timeline

• Start date: 2024-01-18
• Primary completion: 2027-06-01
• Completion: 2028-12-01
• First posted: 2023-12-08
• Last updated: 2026-03-09

Locations

89 sites across 11 countries: United States, Australia, Denmark, France, Germany, Greece, Italy, Netherlands, South Korea, Spain, Taiwan

Regulatory

• FDA-regulated drug study