RecruitingPhase 1Phase 2NCT06162221

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

A Platform Study of RAS(ON) Inhibitors in Patients With RAS-Mutated Non-Small Cell Lung Cancer (NSCLC)


Sponsor

Revolution Medicines, Inc.

Enrollment

616 participants

Start Date

Jan 18, 2024

Study Type

INTERVENTIONAL

Summary

The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors as a monotherapy or combined with Standard(s) of Care (SOC) or with each other. The first four subprotocols include the following: Subprotocol A: RMC-6291 +/- RMC-6236 + SOC Subprotocol B: RMC-6236 + SOC Subprotocol C: RMC-9805 +/- RMC-6236 + SOC Subprotocol D: RMC-9805


Eligibility

Min Age: 18 Years

Inclusion Criteria8

  • 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 KRAS G12C-mutated solid tumor malignancy (not amenable to curative surgery) (Subprotocol A)
  • Must have pathologically documented, locally advanced or metastatic RAS-mutated NSCLC (Subprotocol B)
  • Must have pathologically documented, locally advanced or metastatic RAS G12D-mutated NSCLC (Subprotocol C and Subprotocol D)

Exclusion Criteria5

  • All Patients:
  • Primary central nervous system (CNS) tumors
  • Impaired gastrointestinal (GI) function that may significantly alter the absorption of RMC drugs
  • Major surgery \< 28 days of first dose
  • Active or history of interstitial lung disease (ILD) or pneumonitis requiring steroids

Interventions

DRUGRMC-6291

Oral tablet

DRUGRMC-6236

Oral tablet

DRUGPembrolizumab

IV Infusion

DRUGCisplatin

IV Infusion

DRUGCarboplatin

IV Infusion

DRUGPemetrexed

IV infusion

DRUGRMC-9805

Oral Tablet


Locations(89)

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

City of Hope - Duarte

Duarte, California, United States

City of Hope - Lennar

Irvine, California, United States

UC Davis, Davis Comprehensive Cancer Center

Sacramento, California, United States

University of California, San Diego Moores Cancer Center

San Diego, California, United States

UCSF Medical Center - Mission Bay

San Francisco, California, United States

Stanford University - Stanford Cancer Institute

Stanford, California, United States

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Boca Raton Clinical Research Associates

Plantation, Florida, United States

Cancer Specialists of North Florida

Saint Augustine, Florida, United States

H Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)

Detroit, Michigan, United States

Intermountain Health - St. Vincent Frontier Cancer Center

Billings, Montana, United States

Nebraska Cancer Specialist

Grand Island, Nebraska, United States

New York University Langone Health

New York, New York, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Columbia University Medical Center

New York, New York, United States

Clinical Research Alliance

Westbury, New York, United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Baptist Medical Center

Memphis, Tennessee, United States

Tennessee Oncology

Nashville, Tennessee, United States

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

NEXT Oncology Dallas

Irving, Texas, United States

NEXT Oncology Virginia

Fairfax, Virginia, United States

Chris O'Brien Lifehouse Hosptial

Camperdown, New South Wales, Australia

Liverpool Hospital

Liverpool, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Monash Health

Clayton, Victoria, Australia

Linear Clinical Research

Nedlands, Western Australia, Australia

Rigshospitalet

Copenhagen, Denmark

Odense University Hospital, Department of Oncology

Odense, Denmark

Hospices Civils de Lyon - Hôpital Louis Pradel

Bron, Auvergne-Rhône-Alpes, France

Centre Georges François Leclerc

Dijon, Bourgogne-Franche-Comté, France

CHU de Lille Institut Cœur Poumon

Lille, Hauts-de-France, France

CHU de Nantes

Nantes, Hauts-de-France, France

EDOG - Institut Bergonié

Bordeaux, Nouvelle-Aquitaine, France

Institut de Cancerologie de Ouest (ICO) - Angers

Angers, France

Ambroise-Paré Hospital

Boulogne, France

Centre François Baclesse

Caen, France

Hôpital Cochin

Paris, France

Hopital Tenon - AP-HP

Paris, France

Hopital Foch

Suresnes, France

Oncopole Claudius Regaud

Toulouse, France

Institut Gustave Roussy

Villejuif, France

Institut Curie

Paris, Île-de-France Region, France

Charite-Universitaetsmedizin Berlin - Campus Charite Mitte

Berlin, Germany

Uniklinik Köln

Cologne, Germany

Universitätsklinikum Carl Gustav Carus an der TU Dresden

Dresden, Germany

Universitätsklinikum Frankfurt

Frankfurt am Main, Germany

Thoraxklinik Heidelberg gGmbH - Universitätsklinikum Heidelberg

Heidelberg, Germany

Lungenfachklinik Immenhausen

Immenhausen, Germany

Krankenhaus Bethanien Moers

Moers, Germany

Henry Dunant Hospital Center

Athens, Greece

Thoracic General Hospital of Athens "I SOTIRIA"

Athens, Greece

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

Meldola, Emilia-Romagna, Italy

Fondazione IRCCS Istituto Nazionale dei tumori

Milan, Italy

ASST Grande Ospedale Metropolitano Niguarda

Milan, Italy

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

Orbassano, Italy

Ospedale Santa Maria Delle Croci

Ravenna, Italy

IRCCS Instituto Nazionale tumori Ragina Elena

Rome, Italy

Fondazione Policlinico Universitario A Gemelli-Rome

Rome, Italy

The Netherlands Cancer Institute (NKI)

Amsterdam, Netherlands

University Medical Centre Groningen

Groningen, Netherlands

Leiden University Medical Center

Leiden, Netherlands

University Medical Center Utrecht

Utrecht, Netherlands

Samsung Medical Center

Seoul, Gangnam-gu, South Korea

National Cancer Center

Goyang-si, Gyeonggi-do, South Korea

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggido, South Korea

Seoul St. Mary's Hospital, The Catholic University of Korea

Seoul, Seocho-gu, South Korea

Severance Hospital

Seoul, Seodaemun-Gu, South Korea

Hospital Clinico San Carlos

Madrid, Madrid, Spain

Hospital Universitario 12 de Octubre

Madrid, Madrid, Spain

Clinica Universidad de Navarra

Pamplona, Navarre, Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, Valencia, Spain

Complejo Hospitalario Universitario A Coruña

A Coruña, Spain

Hospital Universitari Vall D' Hebron

Barcelona, Spain

ICO Badalona - H.U. Germans Trias i Pujol

Barcelona, Spain

Hospital Universitario Ramon y Cajal

Madrid, Spain

Hospital Universitario Fundacion Jimenez Diaz

Madrid, Spain

Hospital Regional Universitario de Malaga - Hospital Civil

Málaga, Spain

Hospital Universitario Virgen del Rocio - PPDS

Seville, Spain

Fundacion Instituto Valenciano de Oncologia

Valencia, Spain

Taipei Municipal Wanfang Hospital

Taipei, Wenshan Dist, Taiwan

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, Taiwan

Taichung Veterans General Hospital

Taichung, Taiwan

Chi Mei Hospital, Liouying

Tainan, Taiwan

Taipei Veterans General Hospital

Taipei, Taiwan

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NCT06162221