Study of RAS(ON) Inhibitors in Patients With Advanced RAS-mutated NSCLC
NCT ID: NCT06162221
Last Updated: 2025-11-06
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
616 participants
INTERVENTIONAL
2024-01-18
2028-12-31
Brief Summary
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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
Detailed Description
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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), or as a monotherapy 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)
Subprotocol D is a Phase 2, Open-label, Multicenter Study of Zoldonrasib (RMC-9805) in Previously Treated Patients with RAS G12D-Mutant Non-Small Cell Lung Cancer (NSCLC)
Subprotocols A, B, and C consist of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion. Subprotocol D consists of only one part.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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Subprotocol A: KRAS G12C-Mutated Solid Tumors
RMC-6291 (BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
RMC-6291
Oral tablet
RMC-6236
Oral tablet
Pembrolizumab
IV Infusion
Cisplatin
IV Infusion
Carboplatin
IV Infusion
Pemetrexed
IV infusion
Subprotocol B: RAS-mutated NSCLC
RMC-6236 (QD) and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)
RMC-6236
Oral tablet
Pembrolizumab
IV Infusion
Cisplatin
IV Infusion
Carboplatin
IV Infusion
Pemetrexed
IV infusion
Subprotocol C: RAS G12D-mutated NSCLC
RMC-9805 (QD or BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W).
RMC-6236
Oral tablet
Pembrolizumab
IV Infusion
Cisplatin
IV Infusion
Carboplatin
IV Infusion
Pemetrexed
IV infusion
RMC-9805
Oral Tablet
Subprotocol D: RAS G12D-mutated NSCLC
RMC-9805 (QD)
RMC-9805
Oral Tablet
Interventions
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RMC-6291
Oral tablet
RMC-6236
Oral tablet
Pembrolizumab
IV Infusion
Cisplatin
IV Infusion
Carboplatin
IV Infusion
Pemetrexed
IV infusion
RMC-9805
Oral Tablet
Eligibility Criteria
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Inclusion Criteria
* ≥ 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 Criteria
* 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
18 Years
ALL
No
Sponsors
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Revolution Medicines, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Revolution Medicines
Role: STUDY_DIRECTOR
Revolution Medicines
Locations
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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
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
Linear Clinical Research
Nedlands, Western Australia, Australia
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
Centre François Baclesse
Caen, , 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
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
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
Countries
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Central Contacts
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Facility Contacts
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Taylor Alexander
Role: primary
Stephanie Casal
Role: primary
Thanina Amirat
Role: primary
Kathy Velasco
Role: primary
Role: primary
Role: primary
Shannon Raue
Role: primary
Sandra Perez
Role: primary
Justin Elkins
Role: primary
Ana Aminpour
Role: primary
Thoracic KRAS Referrals
Role: primary
Dalia Abdullah
Role: primary
Heather Duyck
Role: primary
Salman Punekar
Role: primary
Jessica Setal-Hunte
Role: primary
Role: primary
Role: primary
Role: primary
Role: primary
Alison Shaw
Role: primary
Idara Ukpong
Role: primary
Blake Patterson
Role: primary
Raphaële Guelminger
Role: primary
François Ghirighhelli
Role: primary
Eric Wasielewski
Role: primary
Jeanne Chen
Role: primary
Sophie Cousin
Role: primary
Hubert Curcio
Role: primary
Jaafar Bennouna
Role: primary
Audrey Rabeau
Role: primary
Capucine Baldini
Role: primary
Pauline Du Rusquec
Role: primary
Damian Rieke, MD
Role: primary
Role: primary
Max Langner
Role: primary
Role: primary
Role: primary
Svenja Brede
Role: primary
Role: primary
Oriana Nanni
Role: primary
Role: primary
Manolo D'Arcangelo
Role: primary
Oriana Nanni
Role: primary
Role: primary
Role: primary
Role: primary
Bernard Doger
Role: primary
Role: primary
Mariano Ponz Sarvise
Role: primary
Role: primary
Maria Eugenia Olmedo
Role: primary
Role: primary
Alicia Medina
Role: primary
Laura Bernal Iriarte
Role: primary
David Lorente Estellés
Role: primary
References
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Cregg J, Edwards AV, Chang S, Lee BJ, Knox JE, Tomlinson ACA, Marquez A, Liu Y, Freilich R, Aay N, Wang Y, Jiang L, Jiang J, Wang Z, Flagella M, Wildes D, Smith JAM, Singh M, Wang Z, Gill AL, Koltun ES. Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-selective, Noncovalent Tri-complex Inhibitor for the Treatment of Patients with Multiple RAS-Addicted Cancers. J Med Chem. 2025 Mar 27;68(6):6064-6083. doi: 10.1021/acs.jmedchem.4c02314. Epub 2025 Mar 8.
Other Identifiers
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RMC-LUNG-101
Identifier Type: -
Identifier Source: org_study_id