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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06128551
• Other study ID #: RMC-6291-101
• Status: Recruiting
• Phase: Phase 1
• Start date: November 14, 2023
• Est. completion date: November 30, 2026

Study information

• Verified date: June 2024
• Source: Revolution Medicines, Inc.
• Contact: Revolution Medicines, Inc.
• Phone: 650-779-2300
• Email: CT-inquiries[@]RevMed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 210
• Est. completion date: November 30, 2026
• Est. primary completion date: November 30, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 125 Years

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Colorectal Neoplasms
• Lung Neoplasms
• Non-Small Cell Lung Cancer (NSCLC)
• Pancreatic Ductal Adenocarcinoma

Intervention

Drug:
• Assigned interventions
Drug: RMC-6291 and RMC-6236 Oral tablets

Locations

Country	Name	City	State
Puerto Rico	Pan American Center for Oncology Trials	San Juan
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Mary Crowley Cancer Research	Dallas	Texas
United States	NEXT Oncology Virginia	Fairfax	Virginia
United States	START Midwest	Grand Rapids	Michigan
United States	MD Anderson	Houston	Texas
United States	NEXT Dallas	Irving	Texas
United States	Sarah Cannon Research Institue	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	NYU Langone Health	New York	New York
United States	UC Davis Comprehensive Cancer Center	Sacramento	California
United States	NEXT Oncology San Antonio	San Antonio	Texas
United States	START Texas	San Antonio	Texas
United States	Stanford Cancer Institute	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Revolution Medicines, Inc.

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Dose Limiting Toxicities	Number of participants with dose limiting toxicities	21 days
Secondary	Maximum Observed Blood Concentration of RMC-6291 and RMC-6236	Cmax	up to 21 weeks
Secondary	Time to Reach Maximum Blood Concentration of RMC-6291 and RMC-6236	Tmax	up to 21 weeks
Secondary	Area Under Blood Concentration Time Curve of RMC-6291 and RMC-6236	AUC	up to 21 weeks
Secondary	Elimination Half-Life of RMC-6291 and RMC-6236	t1/2	up to 21 weeks
Secondary	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
Secondary	Overall Response Rate (ORR)	Overall response rate RECIST v1.1	up to 3 years
Secondary	Duration of Response (DOR)	Duration of response per RECIST v1.1	up to 3 years
Secondary	Disease Control Rate	Disease Control rate per RECIST v1.1	up to 3 years
Secondary	Time to Response (TTR)	Time to response per RECIST v1.1	up to 3 years
Secondary	Progression-Free Survival (PFS)	Progression-free survival per RECIST v1.1	up to 3 years