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

Last updated: May 5, 2025
Sponsor: Revolution Medicines, Inc.
Overall Status: Active - Recruiting

Phase

1/2

Condition

Neoplasms

Treatment

Pemetrexed

RMC-6291

Pembrolizumab

Clinical Study ID

NCT06162221
RMC-LUNG-101
  • Ages > 18
  • All Genders

Study Summary

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 three subprotocols include the following:

Subprotocol A: RMC-6291 +/- RMC-6236 + SOC Subprotocol B: RMC-6236 + SOC Subprotocol C: RMC-9805 +/- RMC-6236 + SOC

Eligibility Criteria

Inclusion

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 KRASG12C-mutated solid tumor malignancy (not amenable to curative surgery) (SubprotocolA)

  • Must have pathologically documented, locally advanced or metastatic RAS-mutatedNSCLC (Subprotocol B)

  • Must have pathologically documented, locally advanced or metastatic RAS G12D-mutatedNSCLC (Subprotocol C)

Exclusion

Exclusion criteria:

All Patients:

  • Primary central nervous system (CNS) tumors

  • Impaired gastrointestinal (GI) function that may significantly alter the absorptionof RMC drugs

  • Major surgery < 28 days of first dose

  • Active or history of interstitial lung disease (ILD) or pneumonitis requiringsteroids

Other inclusion/exclusion criteria may apply.

Study Design

Total Participants: 484
Treatment Group(s): 7
Primary Treatment: Pemetrexed
Phase: 1/2
Study Start date:
January 18, 2024
Estimated Completion Date:
December 31, 2028

Study 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)

Subprotocol C is an open-label, multicenter, Phase1b/2 study of RMC-9805 with or without RMC-6236, in combination with other anticancer agents, in patients with RAS G12D-mutated non-small cell lung cancer (NSCLC)

Each subprotocol consists of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.

Connect with a study center

  • Hospices Civils de Lyon - Hôpital Louis Pradel

    Bron, Auvergne-Rhône-Alpes 69500
    France

    Active - Recruiting

  • Centre Georges François Leclerc

    Dijon, Bourgogne-Franche-Comté 21079
    France

    Active - Recruiting

  • CHU de Lille Institut Cœur Poumon

    Lille, Hauts-de-France 59037
    France

    Active - Recruiting

  • CHU de Nantes

    Nantes, Hauts-de-France 44093
    France

    Active - Recruiting

  • EDOG - Institut Bergonié

    Bordeaux, Nouvelle-Aquitaine 33000
    France

    Active - Recruiting

  • Institut Curie

    Paris, Île-de-France 75005
    France

    Active - Recruiting

  • Centre François Baclesse

    Caen, 14076
    France

    Active - Recruiting

  • Hopital Foch

    Suresnes, 92150
    France

    Active - Recruiting

  • Oncopole Claudius Regaud

    Toulouse, 31059
    France

    Active - Recruiting

  • Institut Gustave Roussy

    Villejuif, 94805
    France

    Active - Recruiting

  • Charite-Universitaetsmedizin Berlin - Campus Charite Mitte

    Berlin, 12203
    Germany

    Active - Recruiting

  • Universitätsklinikum Carl Gustav Carus an der TU Dresden

    Dresden, 01307
    Germany

    Active - Recruiting

  • Universitätsklinikum Frankfurt

    Frankfurt am Main, 60590
    Germany

    Active - Recruiting

  • Thoraxklinik Heidelberg gGmbH - Universitätsklinikum Heidelberg

    Heidelberg, 69126
    Germany

    Active - Recruiting

  • Lungenfachklinik Immenhausen

    Immenhausen, 34376
    Germany

    Active - Recruiting

  • Uniklinik Köln

    Koln, 50937
    Germany

    Active - Recruiting

  • Krankenhaus Bethanien Moers

    Moers, 47441
    Germany

    Active - Recruiting

  • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l

    Meldola, Emilia-Romagna 47014
    Italy

    Active - Recruiting

  • ASST Grande Ospedale Metropolitano Niguarda

    Milan, 20162
    Italy

    Active - Recruiting

  • Fondazione IRCCS Istituto Nazionale dei tumori

    Milan, 20133
    Italy

    Active - Recruiting

  • A.O.U. San Luigi Gonzaga-Orbassano

    Orbassano, 10043
    Italy

    Active - Recruiting

  • A.O.U. San Luigi Gonzaga-Orbassano - SCDU Oncologia Medica

    Orbassano, 10043
    Italy

    Active - Recruiting

  • Ospedale Santa Maria Delle Croci

    Ravenna, 48121
    Italy

    Active - Recruiting

  • Fondazione Policlinico Universitario A Gemelli-Rome

    Rome, 00168
    Italy

    Active - Recruiting

  • IRCCS Instituto Nazionale tumori Ragina Elena

    Rome, 00144
    Italy

    Active - Recruiting

  • The Netherlands Cancer Institute (NKI)

    Amsterdam, 1066
    Netherlands

    Active - Recruiting

  • University Medical Centre Groningen

    Groningen, 9713
    Netherlands

    Active - Recruiting

  • University Medical Center Utrecht

    Utrecht, 3584
    Netherlands

    Active - Recruiting

  • Hospital Universitario 12 de Octubre

    Madrid, Comunidad de Madrid 28041
    Spain

    Active - Recruiting

  • Clinica Universidad de Navarra

    Pamplona, Navarre 31008
    Spain

    Active - Recruiting

  • Hospital Universitari Vall D' Hebron

    Barcelona, 08035
    Spain

    Active - Recruiting

  • Complejo Hospitalario Universitario A Coruña

    Coruña, 15006
    Spain

    Active - Recruiting

  • Hospital Clinico San Carlos

    Madrid, 28040
    Spain

    Active - Recruiting

  • Hospital Universitario Fundacion Jimenez Diaz

    Madrid, 28040
    Spain

    Active - Recruiting

  • Hospital Universitario Ramon y Cajal

    Madrid, 28034
    Spain

    Active - Recruiting

  • Hospital Regional Universitario de Malaga - Hospital Civil

    Malaga, 29011
    Spain

    Active - Recruiting

  • Hospital Universitario Virgen del Rocio - PPDS

    Sevilla, 41014
    Spain

    Active - Recruiting

  • Fundacion Instituto Valenciano de Oncologia

    Valencia, 46009
    Spain

    Active - Recruiting

  • Hospital Universitari i Politecnic La Fe de Valencia

    Valencia, 46026
    Spain

    Active - Recruiting

  • City of Hope - Duarte

    Duarte, California 91010
    United States

    Active - Recruiting

  • City of Hope - Lennar

    Irvine, California 92618
    United States

    Active - Recruiting

  • UC Davis, Davis Comprehensive Cancer Center

    Sacramento, California 95817
    United States

    Active - Recruiting

  • University of California, San Diego Moores Cancer Center

    San Diego, California 92037
    United States

    Active - Recruiting

  • UCSF Medical Center - Mission Bay

    San Francisco, California 94158
    United States

    Active - Recruiting

  • Stanford University

    Stanford, California 94305
    United States

    Active - Recruiting

  • Stanford University - Stanford Cancer Institute

    Stanford, California 94305
    United States

    Active - Recruiting

  • Georgetown University Medical Center

    Washington, District of Columbia 20007
    United States

    Active - Recruiting

  • Boca Raton Clinical Research Associates

    Plantation, Florida 33322
    United States

    Active - Recruiting

  • Cancer Specialists of North Florida

    Saint Augustine, Florida 32086
    United States

    Site Not Available

  • Cancer Specialists of North Florida

    St Augustine, Florida 32086
    United States

    Active - Recruiting

  • H Lee Moffitt Cancer Center and Research Institute

    Tampa, Florida 33612
    United States

    Active - Recruiting

  • Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)

    Detroit, Michigan 48202
    United States

    Active - Recruiting

  • Intermountain Health - St. Vincent Frontier Cancer Center

    Billings, Montana 59102
    United States

    Active - Recruiting

  • Columbia University Medical Center

    New York, New York 10032
    United States

    Active - Recruiting

  • Icahn School of Medicine at Mount Sinai

    New York, New York 10029
    United States

    Active - Recruiting

  • New York University Langone Health

    New York, New York 10016
    United States

    Active - Recruiting

  • Clinical Research Alliance

    Westbury, New York 11590
    United States

    Active - Recruiting

  • University Hospitals Cleveland Medical Center

    Cleveland, Ohio 44106
    United States

    Active - Recruiting

  • Hillman Cancer Center

    Pittsburgh, Pennsylvania 15232
    United States

    Active - Recruiting

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania 15232
    United States

    Active - Recruiting

  • MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Active - Recruiting

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas 77030
    United States

    Active - Recruiting

  • NEXT Oncology Dallas

    Irving, Texas 75039
    United States

    Active - Recruiting

  • NEXT Oncology Virginia

    Fairfax, Virginia 22031
    United States

    Active - Recruiting

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