Study of RMC-6291 in Combination With RMC-6236 in Participants With Advanced KRAS G12C Mutant Solid Tumors

Phase 1b, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of RMC-6291 in Combination With RMC-6236 in Participants With Advanced KRAS G12C Mutant Solid Tumors

This study is to evaluate the safety, tolerability, and PK profiles of RMC-6291 and RMC-6236 in adults with KRAS G12C-mutated solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Pancreatic Ductal Adenocarcinoma; Non-Small Cell Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: Assigned interventions

Detailed Description

This is an open-label, multicenter, Phase 1b study of RMC-6291 in combination with RMC-6236 in participants with advanced KRAS G12C-mutated solid tumors, to identify the maximum tolerated dose (MTD) and/or recommended Phase 2 dose and schedule (RP2DS) and provide a preliminary assessment of the antitumor activity of RMC-6291 in participants with KRASG12C tumors.

The study consists of two parts: Part 1 - Dose-Escalation and Part 2 Dose-Expansion.

• Study Type: Interventional
• Enrollment (Estimated): 210
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Revolution Medicines, Inc.; Phone Number: 650-779-2300; Email: CT-inquiries@RevMed.com

Study Locations

• United States
  • California
    • Sacramento, California, United States, 95817
      • Recruiting
      • UC Davis Comprehensive Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
  • Texas
    • Irving, Texas, United States, 75039
      • Recruiting
      • Next Dallas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology San Antonio
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • START Texas
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Oncology Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 18 years of age

• Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy

  1. Part 1. Dose Escalation: solid tumors, previously treated
  2. Part 2. Dose Expansion:

  i. NSCLC, previously treated with immunotherapy, chemotherapy, and KRAS G12C (OFF) inhibitors, ii. NSCLC, previously treated with immunotherapy and chemotherapy, naïve to KRAS G12C (OFF) inhibitors, iii. NSCLC, previously treated with immunotherapy, chemotherapy, with untreated, asymptomatic central nervous system (CNS) metastases <2 cm in size iv. Solid tumors, previously treated, naïve to KRAS G12C (OFF) inhibitors.

• ECOG performance status 0 or 1
• Adequate organ function

Exclusion Criteria:

• Primary central nervous system (CNS) tumors
• Active brain metastases
• Known impairment of GI function that would alter the absorption
• Major surgical procedures within 28 days or non-study related minor procedures within 7 days of treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RMC-6291 and RMC-6236; Dose escalation and Dose expansion	Drug: Assigned interventions; Drug: RMC-6291 and RMC-6236 Oral tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs and vitals signs	up to 3 years
Dose Limiting Toxicities	Number of participants with dose limiting toxicities	21 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Observed Blood Concentration of RMC-6291 and RMC-6236	Cmax	up to 21 weeks
Time to Reach Maximum Blood Concentration of RMC-6291 and RMC-6236	Tmax	up to 21 weeks
Area Under Blood Concentration Time Curve of RMC-6291 and RMC-6236	AUC	up to 21 weeks
Elimination Half-Life of RMC-6291 and RMC-6236	t1/2	up to 21 weeks
Ratio of accumulation of RMC-6291 and RMC-6236 from a single dose to steady state with repeated dosing	accumulation ratio	up to 21 weeks
Overall Response Rate (ORR)	Overall response rate RECIST v1.1	up to 3 years
Duration of Response (DOR)	Duration of response per RECIST v1.1	up to 3 years
Disease Control Rate	Disease Control rate per RECIST v1.1	up to 3 years
Time to Response (TTR)	Time to response per RECIST v1.1	up to 3 years
Progression-Free Survival (PFS)	Progression-free survival per RECIST v1.1	up to 3 years

Collaborators and Investigators

• Sponsor: Revolution Medicines, Inc.
• Investigators: Study Director: Revolution Medicines, Inc., Revolution Medicines, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: November 7, 2023
• First Submitted That Met QC Criteria: November 7, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): March 1, 2024
• Last Update Submitted That Met QC Criteria: February 28, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Lung Cancer; NSCLC; Neoplasms; Gastric Cancer; Targeted therapy; Pancreatic Cancer; Colorectal Cancer; Ovarian Cancer; KRAS mutation; STK11/LKB1; KEAP1; Endometrial Cancer; Metastatic Cancer; Esophageal Cancer; Rectal Cancer; Colon Cancer; Non-small Cell Lung Cancer; Thoracic Neoplasms; KRAS; CRC; PDAC; Ampullary Cancer; Intestinal Neoplasms; Gastrointestinal Neoplasms; Gynecological Cancer; Colonic Neoplasms; Lung Neoplasms; Lung disease; RMC-6291; KRASG12C; Carcinoma, Non-Small Cell Lung; Appendiceal Cancer; Carcinoma, Pancreatic Ductal; Neoplasms by site; Respiratory tract diseases; Bronchial neoplasms; RAS (ON); KRASG12C (ON); Respiratory tract neoplasms; RMC-6236
• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms
• Other Study ID Numbers: RMC-6291-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No