Non-Small Cell Lung Cancer, NSCLCPhase 1/2NCT06162221
Study of RAS(ON) Inhibitors in Patients With Advanced RAS-mutated NSCLC
A Phase 1/2 study testing RMC-6291, RMC-6236 and Pembrolizumab in people with Non-Small Cell Lung Cancer, NSCLC and KRAS, NRAS, HRAS-mutated NSCLC, run by Revolution Medicines, Inc. at 98 sites in 13 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer, NSCLC, KRAS, NRAS, HRAS-mutated NSCLC, KRAS G12C-mutated Solid Tumors, Lung Cancer
- What is being tested?
- RMC-6291, RMC-6236 and Pembrolizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 616 participants
- Where
- 98 sitesin 13 countries
- Study dates
- 18 Jan 2024to Dec 2028
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
- Other inclusion/exclusion criteria may apply.
Trial locations and contacts
98 sites in 13 countries. Contact the study team or a site near you to ask about taking part.
98 sites in 13 countries
United States29 sites, 19 recruiting
- Active, not recruiting
Intermountain Health - St. Vincent Frontier Cancer Center
Billings, Montana, 59102
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Thoracic KRAS Referrals, 877-442-3324, dfcitopkrasmetclinicalresearch@partners.org
- Recruiting
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
216-844-3951
- Active, not recruiting
Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)
Detroit, Michigan, 48202
- Active, not recruiting
City of Hope - Duarte
Duarte, California, 91010
- Recruiting
NEXT Oncology Virginia
Fairfax, Virginia, 22031
Blake Patterson, 703-783-4505, bpatterson@nextoncology.com
- Recruiting
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
- Recruiting
Nebraska Cancer Specialist
Grand Island, Nebraska, 68803
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Alison Shaw, 713-563-1235, ANTran1@mdanderson.org
- Active, not recruiting
City of Hope - Lennar
Irvine, California, 92618
- Recruiting
NEXT Oncology Dallas
Irving, Texas, 75039
Idara Ukpong, 972-893-8800, iukpong@nextoncology.com
- Active, not recruiting
University of California Los Angeles
Los Angeles, California, 90095
- Recruiting
Baptist Medical Center
Memphis, Tennessee, 38120
- Recruiting
Tennessee Oncology
Nashville, Tennessee, 37203
- Recruiting
New York University Langone Health
New York, New York, 10016
Salman Punekar, 212-731-6228, Salman.punekar@nyulangone.org
- Active, not recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
- Recruiting
Columbia University Medical Center
New York, New York, 10032
212-342-5162, Cancerclinicaltrials@cumc.columbia.edu
- Recruiting
UPMC Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
iddcreferrals@upmc.edu
- Recruiting
Boca Raton Clinical Research Associates
Plantation, Florida, 33322
Sandra Perez, 561-447-0614, sperez@brcrglobal.com
- Recruiting
UC Davis, Davis Comprehensive Cancer Center
Sacramento, California, 95817
Thanina Amirat, 916-734-3186, tamirat@ucdavis.edu
- Active, not recruiting
Cancer Specialists of North Florida
Saint Augustine, Florida, 32086
- Recruiting
University of California, San Diego Moores Cancer Center
San Diego, California, 92037
Kathy Velasco, 858-822-5677, kcvelasco@health.ucsd.edu
- Recruiting
UCSF Medical Center - Mission Bay
San Francisco, California, 94158
415-866-7866, lisa.tan@ucsf.edu
- Active, not recruiting
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
- Recruiting
Stanford University - Stanford Cancer Institute
Stanford, California, 94305
650-498-6000, secure-thoraciccancertrials@lists.stanford.edu
- Recruiting
H Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
Ana Aminpour, 813-745-0287, anahid.aminpour@moffitt.org
- Active, not recruiting
Kaiser Permanente
Vallejo, California, 94589
- Recruiting
Georgetown University Medical Center
Washington D.C., District of Columbia, 20007
Shannon Raue, 202-784-5097, sr1657@georgetown.edu
- Active, not recruiting
Clinical Research Alliance
Westbury, New York, 11590
France14 sites, 10 recruiting
- Recruiting
Institut de Cancerologie de Ouest (ICO) - Angers
Angers, 49055
- Recruiting
EDOG - Institut Bergonié
Bordeaux, New Aquitaine, 33000
Sophie Cousin, 33 5 56 33 33 33, s.cousin@bordeaux.unicancer.fr
- Active, not recruiting
Ambroise-Paré Hospital
Boulogne, 92104
- Recruiting
Hospices Civils de Lyon - Hôpital Louis Pradel
Bron, Auvergne-Rhône-Alpes, 69500
Raphaële Guelminger, 33 4 72 35 70 74, raphaele.guelminger@chu-lyon.fr
- Recruiting
Centre François Baclesse
Caen, 14076
Hubert Curcio, 33 2 31 45 50 50, h.curcio@baclesse.unicancer.fr
- Recruiting
Centre Georges François Leclerc
Dijon, Bourgogne-Franche-Comté, 21079
François Ghirighhelli, 33 3 80 73 75 06, fghiringhelli@cgfl.fr
- Recruiting
CHU de Lille Institut Cœur Poumon
Lille, Hauts-de-France, 59037
Eric Wasielewski, 33 3 62 94 35 91, eric.wasielewski@chu-lille.fr
- Active, not recruiting
CHU de Nantes
Nantes, Hauts-de-France, 44093
- Recruiting
Hôpital Cochin
Paris, 75014
- Active, not recruiting
Hopital Tenon - AP-HP
Paris, 75020
- Recruiting
Institut Curie
Paris, Île-de-France Region, 75005
Pauline Du Rusquec, 33 1 56 24 58 39, pauline.durusquec@curie.fr
- Active, not recruiting
Hopital Foch
Suresnes, 92150
- Recruiting
Oncopole Claudius Regaud
Toulouse, 31059
Audrey Rabeau, 33 5 31 15 51 64, Rabeau.Audrey@iuct-oncopole.fr
- Recruiting
Institut Gustave Roussy
Villejuif, 94805
Capucine Baldini, 33 3 20 44 54 61, capucine.baldini@gustaveroussy.fr
Spain13 sites, 11 recruiting
- Recruiting
Complejo Hospitalario Universitario A Coruña
A Coruña, 15006
34981178000, ensayos.clinicos.onco.asacec@sergas.es
- Recruiting
Hospital Universitari Vall D' Hebron
Barcelona, 08035
- Active, not recruiting
ICO Badalona - H.U. Germans Trias i Pujol
Barcelona, 08916
- Recruiting
Hospital Clinico San Carlos
Madrid, Madrid, 28040
Bernard Doger, 0034 91 550 4800 ext 2805, fjd@startmadrid.com
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, Madrid, 28041
oncologia.imas12@h12o.es
- Recruiting
Hospital Universitario Ramon y Cajal
Madrid, 28034
Maria Eugenia Olmedo, 34-913-369-159
- Recruiting
Hospital Universitario Fundacion Jimenez Diaz
Madrid, 28040
+34 91 550 4800 ext. 2805, fjd@startmadrid.com
- Active, not recruiting
Hospital Universitario Quironsalud - NEXT Oncology, Madrid
Madrid, 28223
- Recruiting
Hospital Regional Universitario de Malaga - Hospital Civil
Málaga, 29011
Alicia Medina, + 34951308130, oncologia.ensayos.hrum@ibima.eu
- Recruiting
Clinica Universidad de Navarra
Pamplona, Navarre, 31008
Mariano Ponz Sarvise, +34 91 353 19 20, eecc@unav.es
- Recruiting
Hospital Universitario Virgen del Rocio - PPDS
Seville, 41014
Laura Bernal Iriarte, +34 913 369 159, lauraonco.huvr@gmail.com
- Recruiting
Hospital Universitari i Politecnic La Fe de Valencia
Valencia, Valencia, 46026
- Recruiting
Fundacion Instituto Valenciano de Oncologia
Valencia, 46009
David Lorente Estellés, +34 961114229, dlorente@fivo.org
Italy8 sites, 3 recruiting
- Recruiting
Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l
Meldola, Emilia-Romagna, 47014
Oriana Nanni, oriana.nanni@irst.emr.it
- Recruiting
Fondazione IRCCS Istituto Nazionale dei tumori
Milan, 20133
- Active, not recruiting
Instituto Europeo Di Oncologia
Milan, 20141
- Active, not recruiting
ASST Grande Ospedale Metropolitano Niguarda
Milan, 20162
- Active, not recruiting
A.O.U. San Luigi Gonzaga-Orbassano - SCDU Oncologia Medica
Orbassano, 10043
- Recruiting
Ospedale Santa Maria Delle Croci
Ravenna, 48121
Manolo D'Arcangelo, +39(0)544 287142, manolo.darcangelo@auslromagna.it
- Active, not recruiting
IRCCS Instituto Nazionale tumori Ragina Elena
Rome, 00144
- Active, not recruiting
Fondazione Policlinico Universitario A Gemelli-Rome
Rome, 00168
Germany7 sites, 5 recruiting
- Recruiting
Charite-Universitaetsmedizin Berlin - Campus Charite Mitte
Berlin, 12203
Damian Rieke, MD, +49 30 450 513 470, damian.rieke@charite.de
- Recruiting
Uniklinik Köln
Cologne, 50937
lungenkrebs@uk-koeln.de
- Recruiting
Universitätsklinikum Carl Gustav Carus an der TU Dresden
Dresden, 01307
Max Langner, +49 351 458 7566, ectu@ukdd.de
- Recruiting
Universitätsklinikum Frankfurt
Frankfurt am Main, 60590
+49 696301 80429, silvia.koss@unimedizin-ffm.de
- Recruiting
Thoraxklinik Heidelberg gGmbH - Universitätsklinikum Heidelberg
Heidelberg, 69126
Studienkoordination-Onkologie.THOR@med.uni-heidelberg.de
- Active, not recruiting
Lungenfachklinik Immenhausen
Immenhausen, 34376
- Active, not recruiting
Krankenhaus Bethanien Moers
Moers, 47441
Australia5 sites
- Active, not recruiting
Chris O'Brien Lifehouse Hosptial
Camperdown, New South Wales, 2050
- Active, not recruiting
Monash Health
Clayton, Victoria, 3168
- Active, not recruiting
Liverpool Hospital
Liverpool, New South Wales, 2170
- Active, not recruiting
Linear Clinical Research
Nedlands, Western Australia, 6009
- Active, not recruiting
Royal North Shore Hospital
St Leonards, New South Wales, 2065
South Korea5 sites
- Active, not recruiting
National Cancer Center
Goyang-si, Gyeonggi-do, 10408
- Active, not recruiting
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggido, 13620
- Active, not recruiting
Samsung Medical Center
Seoul, Gangnam-gu, 06351
- Active, not recruiting
Seoul St. Mary's Hospital, The Catholic University of Korea
Seoul, Seocho-gu, 06591
- Active, not recruiting
Severance Hospital
Seoul, Seodaemun-Gu, 03722
Taiwan5 sites
- Active, not recruiting
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung City, 807
- Active, not recruiting
Taichung Veterans General Hospital
Taichung, 40705
- Active, not recruiting
Chi Mei Hospital, Liouying
Tainan, 73657
- Active, not recruiting
Taipei Municipal Wanfang Hospital
Taipei, Wenshan Dist, 116
- Active, not recruiting
Taipei Veterans General Hospital
Taipei, 11217
Netherlands4 sites, 3 recruiting
- Recruiting
The Netherlands Cancer Institute (NKI)
Amsterdam, 1066
0031 (0)20-512 9111, fase1@nki.nl
- Active, not recruiting
University Medical Centre Groningen
Groningen, 9713
- Recruiting
Leiden University Medical Center
Leiden, 2333 ZA
- Recruiting
University Medical Center Utrecht
Utrecht, 3584
+3188 755 6263, oncostudies@umcutrecht.nl
Greece3 sites
- Active, not recruiting
Henry Dunant Hospital Center
Athens, 115 26
- Active, not recruiting
Thoracic General Hospital of Athens "I SOTIRIA"
Athens, 11527
- Active, not recruiting
General Hospital of Thessaloniki
Thessaloniki, 570 10
Austria2 sites
- Active, not recruiting
Universitätsklinikum St. Pölten
Sankt Pölten, Austria, 3100
- Active, not recruiting
Wiener Gesundheitsverbund - Klinik Floridsdorf
Vienna, 1210
Denmark2 sites, 2 recruiting
- Recruiting
Rigshospitalet
Copenhagen, 2100
- Recruiting
Odense University Hospital, Department of Oncology
Odense, 5000
Czechia1 site
- Active, not recruiting
Nemocnice AGEL Novy Jicin a.s
Nový Jičín, Czech Republic, 741 01
About this study
Official title: A Platform Study of RAS(ON) Inhibitors in Patients With RAS-Mutated Non-Small Cell Lung Cancer (NSCLC)
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
Read the detailed description
The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents or as a monotherapy 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), 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
- Non-Small Cell Lung Cancer, NSCLC, KRAS, NRAS, HRAS-mutated NSCLC, KRAS G12C-mutated Solid Tumors, Lung Cancer, Lung Cancer Stage IV, Advanced Solid Tumor, Cancer, RAS G12D-mutated NSCLC
- Being tested
- RMC-6291, RMC-6236, Pembrolizumab, Cisplatin, Carboplatin
- Keywords
- NSCLC, KRAS G12C, RAS Mutation, KRAS G12X, Non-Small Cell Lung Cancer, Lung Cancer, Lung Cancer Stage IV, Advanced Solid Tumor, Cancer, RAS G12D
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RMC-6291Drug
Oral tablet
RMC-6236Drug
Oral tablet
PembrolizumabDrug
IV Infusion
CisplatinDrug
IV Infusion
CarboplatinDrug
IV Infusion
PemetrexedDrug
IV infusion
RMC-9805Drug
Oral Tablet
| Study group | Role | What they receive |
|---|---|---|
| Subprotocol A: KRAS G12C-Mutated Solid Tumors | Experimental | RMC-6291 (BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W) Receives: Drug: RMC-6291; Drug: RMC-6236; Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed |
| Subprotocol B: RAS-mutated NSCLC | Experimental | RMC-6236 (QD) and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W) Receives: Drug: RMC-6236; Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed |
| Subprotocol C: RAS G12D-mutated NSCLC | Experimental | RMC-9805 (QD or BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W). Receives: Drug: RMC-6236; Drug: Pembrolizumab; Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed; Drug: RMC-9805 |
| Subprotocol D: RAS G12D-mutated NSCLC | Experimental | RMC-9805 (QD) Receives: Drug: RMC-9805 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse events
Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs and vital signs
Measured: Up to 5 years
Dose limiting toxicities
Number of participants with dose limiting toxicities
Measured: 21 days
Secondary outcomes (6)
Drug concentrations over time
Observed blood concentration of each drug as applicable per subprotocol
Measured: Up to 21 weeks
Cmax
Maximum observed blood concentration of each drug as applicable per subprotocol
Measured: Up to 21 weeks
Tmax
Time to reach maximum blood concentration of each drug as applicable per subprotocol
Measured: Up to 21 weeks
AUC
Area under the concentration-time curve of each drug as applicable per subprotocol
Measured: Up to 21 weeks
ORR
Objective Response Rate per RECIST v1.1
Measured: Up to 5 years
DOR
Duration of Response per RECIST v1.1
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2023
- Study start18 Jan 2024
- Primary completionJun 2027 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Non-Small Cell Lung Cancer, NSCLCStudies of the same condition, open and under way.
- More trials run by Revolution Medicines, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 616 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Revolution Medicines, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Revolution Medicines, Study director, Revolution Medicines
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06162221
- Sponsor's protocol ID
- RMC-LUNG-101
- Status last verified
- Jun 2026
- First submitted
- 30 Nov 2023
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
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.
PubMed 40056080