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

Phase 1
Recruiting
Conditions
Colorectal Cancer
Pancreatic Ductal Adenocarcinoma
Non-Small Cell Lung Cancer (NSCLC)
Interventions
Drug: Assigned interventions
Registration Number
NCT06128551
Lead Sponsor
Revolution Medicines, Inc.
Brief 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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
210
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
RMC-6291 and RMC-6236Assigned interventionsDose escalation and Dose expansion
Primary Outcome Measures
NameTimeMethod
Adverse eventsup to 3 years

Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs and vitals signs

Dose Limiting Toxicities21 days

Number of participants with dose limiting toxicities

Secondary Outcome Measures
NameTimeMethod
Maximum Observed Blood Concentration of RMC-6291 and RMC-6236up to 21 weeks

Cmax

Time to Reach Maximum Blood Concentration of RMC-6291 and RMC-6236up to 21 weeks

Tmax

Area Under Blood Concentration Time Curve of RMC-6291 and RMC-6236up to 21 weeks

AUC

Ratio of accumulation of RMC-6291 and RMC-6236 from a single dose to steady state with repeated dosingup to 21 weeks

accumulation ratio

Disease Control Rateup to 3 years

Disease Control rate per RECIST v1.1

Duration of Response (DOR)up to 3 years

Duration of response per RECIST v1.1

Time to Response (TTR)up to 3 years

Time to response per RECIST v1.1

Elimination Half-Life of RMC-6291 and RMC-6236up to 21 weeks

t1/2

Overall Response Rate (ORR)up to 3 years

Overall response rate RECIST v1.1

Progression-Free Survival (PFS)up to 3 years

Progression-free survival per RECIST v1.1

Trial Locations

Locations (53)

Niguarda Cancer Center

🇮🇹

Milano, Italy

City of Hope

🇺🇸

Duarte, California, United States

UC IRVINE Health

🇺🇸

Orange, California, United States

UC Davis Comprehensive Cancer Center

🇺🇸

Sacramento, California, United States

Stanford Cancer Institute

🇺🇸

Stanford, California, United States

University of Colorado Cancer Center

🇺🇸

Aurora, Colorado, United States

Florida Cancer Specialists

🇺🇸

Sarasota, Florida, United States

Moffitt Cancer Center and Research Institute

🇺🇸

Tampa, Florida, United States

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Henry Ford Cancer

🇺🇸

Detroit, Michigan, United States

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Niguarda Cancer Center
🇮🇹Milano, Italy

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