Non-small Cell Lung Cancer (NSCLC)Phase 1NCT07349537
Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors
A Phase 1 study testing RMC-5127, daraxonrasib and cetuximab in people with Non-small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC), run by Revolution Medicines, Inc. at 9 sites in United States.
Trial summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RMC-5127 as a monotherapy and in combination with either daraxonrasib or cetuximab in adults with KRAS G12V-mutant 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 (CRC), Pancreatic Adenocarcinoma
- What is being tested?
- RMC-5127, daraxonrasib and cetuximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 574 participants
- Where
- 9 sitesUnited States
- Study dates
- 8 Jan 2026to Oct 2028
- Phase
- Phase 1
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
- At least 18 years old and has provided informed consent.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Pathologically documented, locally advanced or metastatic KRAS G12V-mutated solid tumor malignancy.
- Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage.
- Measurable per RECIST v1.1
- Adequate organ function (bone marrow, liver, kidney, coagulation).
- Able to take oral medications.
Who cannot join
- Primary central nervous system (CNS) tumors
- Prior therapy with KRAS G12V inhibitor or direct RAS-targeted therapy (eg. degraders and/or inhibitors).
- Any conditions that may affect the ability to take or absorb study drug.
- Major surgery within 28 days prior to receiving study drug(s).
- Patient is unable or unwilling to comply with protocol-required study visits or procedures.
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
United States9 sites, 9 recruiting
- Recruiting
Johns Hopkins
Baltimore, Maryland, 21231
Clinical Trials Contact, phase1trials@jh.edu
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Kailene Sullivan, 617-632-3482, kailene_sullivan@dfci.harvard.edu
- Recruiting
NEXT - Dallas
Dallas, Texas, 75039
NEXT TXReferrels, 972-893-8800, NXT_TXReferrals@nextoncology.com
- Recruiting
NEXT - Virginia
Fairfax, Virginia, 22031
Paolo Umayam, 703-783-4546, pumayam@nextoncology.com
- Recruiting
START Midwest
Grand Rapids, Michigan, 49546
616-954-5554 ext. ext. 4, hopeteam@startresearch.com
- Recruiting
Yale Cancer Center
New Haven, Connecticut, 06511
Ingrid Palma, 203-833-1034, ingrid.palma@yale.edu
- Recruiting
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
Salman Punekar, 212-731-6228, salman.punekar@nyulangone.org
- Recruiting
NEXT
San Antonio, Texas, 78229
Jordan Georg, 210-580-9521, jgeorg@nextoncology.com
- Recruiting
START - San Antonio
San Antonio, Texas, 78229
HOPE Team, 210-593-5250, hopeteam@startresearch.com
About this study
Official title: Phase 1/1b, Multicenter, Open-Label, Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RMC-5127 as a monotherapy and in combination with either daraxonrasib or cetuximab in adults with KRAS G12V-mutant solid tumors.
Read the detailed description
This is an open-label, multicenter, Phase 1/1b study of RMC-5127 in adults with advanced KRAS G12V-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of three arms: RMC-5127 monotherapy arm, RMC-5127 plus daraxonrasib combination arm, and RMC-5127 plus cetuximab combination arm. All arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion. Both parts of the monotherapy arm may include Food Effect Cohorts.
- Conditions
- Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Adenocarcinoma, Pancreatic Ductal Adenocarcinoma (PDAC), PDAC, CRC
- Being tested
- RMC-5127, daraxonrasib, cetuximab
- Keywords
- Advanced Solid Tumors, Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma, PDAC, Colorectal Cancer, CRC, Lung Cancer, Non-small Cell Lung Cancer, NSCLC, RAS, KRAS, RAS Mutation
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Pancreatic Neoplasms, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RMC-5127Drug
oral tablets
daraxonrasibDrug
oral tablets
cetuximabDrug
IV infusion
| Study group | Role | What they receive |
|---|---|---|
| Arm A: RMC-5127 Monotherapy | Experimental | Dose Escalation and Dose Expansion Receives: Drug: RMC-5127 |
| Arm B: RMC-5127 + Daraxonrasib Combination | Experimental | Dose Escalation and Dose Expansion Receives: Drug: RMC-5127; Drug: daraxonrasib |
| Arm C: RMC-5127 + Cetuximab Combination | Experimental | Dose Escalation and Dose Expansion Receives: Drug: RMC-5127; Drug: cetuximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with adverse events (AEs)
Number of patients with AEs as assessed by Common Terminology Criteria for Adverse Events CTCAE v5
Measured: Up to approximately 3 years
Changes in vital signs
Number of patients with changes from baseline in vital signs
Measured: Up to approximately 3 years
Changes in electrocardiogram (ECG) test values
Number of patients with changes from baseline in ECG test values
Measured: Up to approximately 3 years
Changes in clinical laboratory test values
Number of patients with changes from baseline in clinical laboratory test values
Measured: Up to approximately 3 years
Dose Limiting Toxicities
Number of patients with dose limiting toxicities
Measured: Up to 28 days
Secondary outcomes (7)
Cmax concentrations of RMC-5127 and daraxonrasib
Maximum blood concentration (Cmax) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and Cmax of daraxonrasib in combination with RMC-5127 over time as applicable
Measured: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Tmax concentration of RMC-5127 and daraxonrasib
Time to reach maximum blood concentration (Tmax) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and Tmax of daraxonrasib in combination with RMC-5127 over time as applicable
Measured: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
AUC concentrations of RMC-5127 and daraxonrasib
Area under the blood concentration time curve (AUC) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and AUC of daraxonrasib in combination with RMC-5127 over time as applicable
Measured: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Ratio of accumulation of RMC-5127
Ratio of accumulation of RMC-5127 from a single dose to steady state with repeated dosing as monotherapy and in combination with darabxrasib or cetuximab over time as applicable
Measured: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Half-Life of RMC-5127 and daraxonrasib
Elimination Half-Life (t1/2) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and t1/2 of daraxonrasib in combination with RMC-5127 over time as applicable
Measured: Up to Cycle 5 Day 1 (each cycle is up to 28 days)
Objective Response Rate (ORR)
ORR per response evaluation criteria in solid tumors (RECIST) v1.1
Measured: Up to approximately 3 years
Duration of Response (DOR)
DOR per RECIST v1.1
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 posted16 Jan 2026
- Study start8 Jan 2026
- Primary completionApr 2028 (estimated)
- Study completionOct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 574 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Revolution Medicines, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07349537
- Sponsor's protocol ID
- RMC-5127-001
- Status last verified
- Sep 2026
- First submitted
- 9 Jan 2026
- Last updated
- 17 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No