Study of RAS(ON) Inhibitor Combinations in Patients with Advanced RAS-mutated NSCLC

Purpose

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

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

All Patients (unless otherwise noted): - ≥ 18 years of age - ECOG PS is 0 to 1 - Adequate organ function as outlined by the study - Received prior standard therapy appropriate for tumor type and stage - Must have pathologically documented, locally advanced or metastatic KRAS G12C-mutated solid tumor malignancy (not amenable to curative surgery) (Subprotocol A) - Must have pathologically documented, locally advanced or metastatic RAS-mutated NSCLC (Subprotocol B)

Exclusion Criteria

All Patients: - Primary central nervous system (CNS) tumors - Impaired gastrointestinal (GI) function that may significantly alter the absorption of RMC drugs - Major surgery < 28 days of first dose - Active or history of interstitial lung disease (ILD) or pneumonitis requiring steroids Other inclusion/exclusion criteria may apply.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Subprotocol A: KRAS G12C-Mutated Solid Tumors 		RMC-6291 (BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W-Q4W)
  • 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
Experimental
Subprotocol B: RAS-mutated NSCLC 		RMC-6236 (QD) and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W-Q4W)
  • Drug: RMC-6236
    Oral tablet
  • Drug: Pembrolizumab
    IV Infusion
  • Drug: Cisplatin
    IV Infusion
  • Drug: Carboplatin
    IV Infusion
  • Drug: Pemetrexed
    IV infusion

Recruiting Locations

Georgetown University Medical Center
Washington, District of Columbia 20007

More Details

Status
Recruiting
Sponsor
Revolution Medicines, Inc.

Study Contact

Revolution Medicines
1-844-2-REVMED
medinfo@RevMed.com

Detailed Description

The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents 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), 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) Each subprotocol consists of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.