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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

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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
Read More

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

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

Disease Control Rateup to 3 years

Disease Control rate per RECIST v1.1

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

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

Trial Locations

Locations (53)

City of Hope

🇺🇸

Duarte, California, United States

UC IRVINE Health

🇺🇸

Orange, California, United States

University of Colorado Cancer Center

🇺🇸

Aurora, Colorado, United States

Moffitt Cancer Center and Research Institute

🇺🇸

Tampa, Florida, United States

Henry Ford Cancer

🇺🇸

Detroit, Michigan, United States

Medical College of Wisconsin

🇺🇸

Milwaukee, Wisconsin, United States

Institut Bergonie

🇫🇷

Bordeaux, France

Hospital Louise Pradel

🇫🇷

Bron, France

Oscar Lambret Center of Lillle

🇫🇷

Lille, France

Centre Leon Berard

🇫🇷

Lyon, France

CHU Nantes

🇫🇷

Nantes, France

Institute of Cancer of Strasbourg

🇫🇷

Strasbourg, France

Klinikum Esslingen GmbH

🇩🇪

Esslingen, Germany

Krankenhaus Bethanien Moers

🇩🇪

Moers, Germany

Klinkum Nurnberg Paracelsus Medical Unviersity

🇩🇪

Nurnberg, Germany

Centro Di Riferimento Oncologico

🇮🇹

Aviano, Italy

S.C. Oncologic Falck

🇮🇹

Milano, Italy

Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale"

🇮🇹

Napoli, Italy

San Luigi Hospital

🇮🇹

Orbassano, Italy

Institut Catala d'Oncologia Hospital

🇪🇸

Barcelona, Spain

Fundacion MD Anderson Cancer Center

🇪🇸

Madrid, Spain

START Madrid

🇪🇸

Madrid, Spain

Hosptial Universitario 12 de Octubre

🇪🇸

Madrid, Spain

Hosptial Universitario Virgen Macarena

🇪🇸

Sevilla, Spain

Hospital Universitario Miguel Servet

🇪🇸

Zaragoza, Spain

UC Davis Comprehensive Cancer Center

🇺🇸

Sacramento, California, United States

Stanford Cancer Institute

🇺🇸

Stanford, California, United States

Florida Cancer Specialists

🇺🇸

Sarasota, Florida, United States

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

START Midwest

🇺🇸

Grand Rapids, Michigan, United States

Columbia University

🇺🇸

New York, New York, United States

NYU Langone Health

🇺🇸

New York, New York, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

University of Oklahoma

🇺🇸

Oklahoma City, Oklahoma, United States

Sarah Cannon Research Institue

🇺🇸

Nashville, Tennessee, United States

Mary Crowley Cancer Research

🇺🇸

Dallas, Texas, United States

MD Anderson

🇺🇸

Houston, Texas, United States

NEXT Dallas

🇺🇸

Irving, Texas, United States

NEXT Oncology San Antonio

🇺🇸

San Antonio, Texas, United States

START Texas

🇺🇸

San Antonio, Texas, United States

NEXT Oncology Virginia

🇺🇸

Fairfax, Virginia, United States

West Cancer Institute

🇫🇷

Angers, France

Cancer Institute of Montpellier

🇫🇷

Montpellier, France

Universitäts Klinikum Köln

🇩🇪

Köln, Germany

Department of Medical Oncology - Azienda Ospedaliero Uniersitaria delle Marche

🇮🇹

Ancona, Italy

Institute Romagnolo per lo Studio Tumori

🇮🇹

Meldola, Italy

AUSL Romagna - S.M. delle Croci Hospital

🇮🇹

Ravenna, Italy

Netherlands Cancer Institute Antoni van Leeuwenhoek

🇳🇱

Amsterdam, Netherlands

Pan American Center for Oncology Trials

🇵🇷

San Juan, Puerto Rico

START Barcelona - Hospital HM Nou Delfos

🇪🇸

Barcelona, Spain

University Clinic of Navarra

🇪🇸

Pamplona, Spain

NEXT Oncology - Quirónsalud Madrid University Hospital

🇪🇸

Madrid, Spain

La Fe University and Polytechnic Hospital

🇪🇸

Valencia, Spain

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