Non-Small Cell Lung Cancer (NSCLC)Phase 1/2NCT06128551
Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid Tumors
A Phase 1/2 study testing Elironrasib and Daraxonrasib in people with Non-Small Cell Lung Cancer (NSCLC) and Colorectal Cancer, run by Revolution Medicines, Inc. at 56 sites in 7 countries.
Trial summary
This study is to evaluate the safety, tolerability, and PK profiles of Elironrasib and Daraxonrasib as monotherapies and combination therapy in patients with KRAS G12C-mutated solid tumors. 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), Colorectal Cancer, Pancreatic Ductal Adenocarcinoma
- What is being tested?
- Elironrasib and Daraxonrasib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 534 participants
- Where
- 56 sitesin 7 countries
- Study dates
- 14 Nov 2023to Jun 2029
- 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
- 18 years of age
- Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy
- Phase 1b Dose Escalation: solid tumors, previously treated
- Phase 1b Dose Expansion and Phase 2:
- NSCLC, previously treated with immunotherapy, chemotherapy, and KRAS G12C (OFF) inhibitors ii. Solid tumors, previously treated, naïve to KRAS G12C (OFF) inhibitors.
- ECOG performance status 0 or 1
- Adequate organ function
Who cannot join
- 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
Trial locations and contacts
56 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
56 sites in 7 countries
United States23 sites, 20 recruiting
- Recruiting
University of Colorado Cancer Center
Aurora, Colorado, 80045
- Recruiting
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
- Completed
Mary Crowley Cancer Research
Dallas, Texas, 75230
- Withdrawn
Henry Ford Cancer
Detroit, Michigan, 48202
- Withdrawn
City of Hope
Duarte, California, 91010
- Recruiting
NEXT Oncology Virginia
Fairfax, Virginia, 22031
- Recruiting
START Midwest
Grand Rapids, Michigan, 49546
- Recruiting
MD Anderson
Houston, Texas, 77030
- Recruiting
Community Health Network
Indianapolis, Indiana, 46250
- Recruiting
NEXT Dallas
Irving, Texas, 75039
- Recruiting
Sarah Cannon Research Institue
Nashville, Tennessee, 37203
- Recruiting
Columbia University
New York, New York, 10032
- Recruiting
NYU Langone Health
New York, New York, 10032
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
- Recruiting
University of Oklahoma
Oklahoma City, Oklahoma, 73104
- Recruiting
UC IRVINE Health
Orange, California, 92868
- Recruiting
Allegheny Health Network
Pittsburgh, Pennsylvania, 15212
- Recruiting
UC Davis Comprehensive Cancer Center
Sacramento, California, 95817
- Recruiting
NEXT Oncology San Antonio
San Antonio, Texas, 78229
- Recruiting
START Texas
San Antonio, Texas, 78229
- Recruiting
Florida Cancer Specialists
Sarasota, Florida, 34232
- Recruiting
Stanford Cancer Institute
Stanford, California, 94305
- Recruiting
Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
Spain11 sites, 11 recruiting
- Recruiting
START Barcelona - Hospital HM Nou Delfos
Barcelona, 08023
- Recruiting
Institut Catala d'Oncologia Hospital
Barcelona, 08908
- Recruiting
University Clinic of Navarra
Madrid, 28027
- Recruiting
Fundacion MD Anderson Cancer Center
Madrid, 28033
- Recruiting
START Madrid
Madrid, 28040
- Recruiting
Hospital Universitario 12 de Octubre
Madrid, 28041
- Recruiting
NEXT Oncology - Quirónsalud Madrid University Hospital
Madrid, 28223
- Recruiting
University Clinic of Navarra
Pamplona, 31008
- Recruiting
Hospital Universitario Virgen Macarena
Seville, 41009
- Recruiting
La Fe University and Polytechnic Hospital
Valencia, 46026
- Recruiting
Hospital Universitario Miguel Servet
Zaragoza, 50009
France8 sites, 7 recruiting
- Recruiting
West Cancer Institute
Angers, 49055
- Recruiting
Institut Bergonie
Bordeaux, 33000
- Recruiting
Hospital Louise Pradel
Bron, 69500
- Recruiting
Oscar Lambret Center of Lillle
Lille, 59000
- Recruiting
Centre Leon Berard
Lyon, 69373
- Recruiting
Cancer Institute of Montpellier
Montpellier, 34298
- Recruiting
CHU Nantes
Nantes, 44093
- Withdrawn
Institute of Cancer of Strasbourg
Strasbourg, 67033
Italy8 sites, 8 recruiting
- Recruiting
Department of Medical Oncology - Azienda Ospedaliero Uniersitaria delle Marche
Ancona, 60126
- Recruiting
Centro Di Riferimento Oncologico
Aviano, 33081
- Recruiting
Institute Romagnolo per lo Studio Tumori
Meldola, 47014
- Recruiting
Niguarda Cancer Center
Milan, 20162
- Recruiting
Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale"
Naples, 80131
- Recruiting
San Luigi Hospital
Orbassano, 10043
- Recruiting
AUSL Romagna - S.M. delle Croci Hospital
Ravenna, 48121
- Recruiting
Centro Ricerche Cliniche di Verona Srl
Verona, Veneto, 37134
Germany4 sites, 4 recruiting
- Recruiting
Universitäts Klinikum Köln
Cologne, 80937
- Recruiting
Klinikum Esslingen GmbH
Esslingen am Neckar, 73730
- Recruiting
Krankenhaus Bethanien Moers
Moers, 47441
- Recruiting
Klinkum Nurnberg Paracelsus Medical Unviersity
Nuremberg, 90419
Netherlands1 site, 1 recruiting
- Recruiting
Netherlands Cancer Institute Antoni van Leeuwenhoek
Amsterdam, 1066CX
Puerto Rico1 site, 1 recruiting
- Recruiting
Pan American Center for Oncology Trials
San Juan, Puerto Rico, 00935
About this study
Official title: Phase 1b/2, Multicenter, Open-label, Dose Escalation and Dose Expansion Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Patients With Advanced KRAS G12C-Mutated Solid Tumors
This study is to evaluate the safety, tolerability, and PK profiles of Elironrasib and Daraxonrasib as monotherapies and combination therapy in patients with KRAS G12C-mutated solid tumors.
Read the detailed description
This is an open-label, multicenter, Phase 1b/2 study evaluating elironrasib and daraxonrasib, administered as monotherapy and in combination, in patients with advanced KRAS G12C-mutated solid tumors to determine the maximum tolerated dose (MTD), identify the recommended Phase 2 dose and schedule (RP2DS), and preliminarily assess antitumor activity.
The study includes a Phase 1b dose escalation and expansion of combination therapy, followed by a Phase 2 evaluation of the selected RP2DS as monotherapy and combination therapy to further assess safety and antitumor activity.
- Being tested
- Elironrasib, Daraxonrasib
- Keywords
- RMC-6291, RAS (ON), KRAS, KRASG12C, KRASG12C (ON), Targeted therapy, Metastatic Cancer, Lung Cancer, Lung Neoplasms, Thoracic Neoplasms, Non-small Cell Lung Cancer, Carcinoma, Non-Small Cell Lung, NSCLC, Colorectal Cancer, Colonic Neoplasms, CRC, Appendiceal Cancer, KRAS mutation, STK11/LKB1, KEAP1
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Neoplasm Metastasis, Lung Neoplasms, Thoracic Neoplasms, Colonic Neoplasms, Appendiceal Neoplasms, Bronchial Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ElironrasibDrug
Also called RMC-6291
oral tablets
DaraxonrasibDrug
Also called RMC-6236
oral tablets
| Study group | Role | What they receive |
|---|---|---|
| Elironrasib Monotherapy | Experimental | Phase 2 only Receives: Drug: Elironrasib |
| Daraxonrasib Monotherapy | Experimental | Phase 2 only Receives: Drug: Daraxonrasib |
| Daraxonrasib + Elironrasib Combination | Experimental | Phase 1b and 2 Receives: Drug: Elironrasib; Drug: Daraxonrasib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with adverse events (AEs) in Phase 1b
Incidence and severity of treatment-emergent AEs and serious AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5
Measured: Up to approximately 3 years
Changes in vital signs in Phase 1b
Number of patients with clinically significant changes in vital signs
Measured: Up to approximately 3 years
Changes in clinical laboratory test values in Phase 1b
Number of patients with clinically significant changes in clinical laboratory test values
Measured: Up to approximately 3 years
Dose Limiting Toxicities in Phase 1b
Number of participants with dose limiting toxicities
Measured: 21 days
Changes in ECGs in Phase 1b
Number of patients with clinically significant changes in ECGs
Measured: Up to approximately 3 years
Overall Response Rate (ORR) in Phase 2
Overall response rate per RECIST v1.1 as assessed by blinded independent central review (BICR)
Measured: Up to approximately 3 years
Secondary outcomes (14)
Maximum Observed Blood Concentration of Elironrasib and Daraxonrasib
Cmax
Measured: up to 21 weeks
Time to Reach Maximum Blood Concentration of Elironrasib and Daraxonrasib
Tmax
Measured: up to 21 weeks
Area Under Blood Concentration Time Curve of Elironrasib and Daraxonrasib
AUC
Measured: up to 21 weeks
Elimination Half-Life of Elironrasib and Daraxonrasib
t1/2
Measured: up to 21 weeks
Ratio of accumulation of Elironrasib and Daraxonrasib from a single dose to steady state with repeated dosing
accumulation ratio
Measured: up to 21 weeks
Overall Response Rate (ORR) in Phase 1b
Overall response rate per RECIST v1.1
Measured: Up to approximately 3 years
Duration of Response (DOR)
Duration of response per RECIST v1.1
Measured: Up to approximately 3 years
Disease Control Rate in Phase 1b
Disease Control rate per RECIST v1.1
Measured: Up to approximately 3 years
Time to Response (TTR) in Phase 1b
Time to response per RECIST v1.1
Measured: Up to approximately 3 years
Progression-Free Survival (PFS)
Progression-free survival per RECIST v1.1
Measured: Up to approximately 3 years
Number of patients with AEs in Phase 2
Incidence and severity of treatment-emergent AEs and serious AEs as assessed by CTCAE v5
Measured: Up to approximately 3 years
Changes in vital signs in Phase 2
Number of patients with clinically significant changes in vital signs
Measured: Up to approximately 3 years
Changes in clinical laboratory values in Phase 2
Number of patients with clinically significant changes in clinical laboratory test values
Measured: Up to approximately 3 years
Overall Survival (OS) in Phase 2
OS is defined as time from enrollment until death from any cause
Measured: Up to approximately 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2023
- Study start14 Nov 2023
- Primary completionDec 2028 (estimated)
- Study completionJun 2029 (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 (NSCLC)Studies 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 534 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Revolution Medicines, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Revolution Medicines, Inc., Study director, Revolution Medicines, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06128551
- Sponsor's protocol ID
- RMC-6291-101
- Status last verified
- Sep 2026
- First submitted
- 7 Nov 2023
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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