Non-small Cell Lung Cancer (NSCLC)Phase 1NCT06040541
Study of RMC-9805 in Participants With KRAS G12D-Mutant Solid Tumors
A Phase 1 study testing RMC-9805 and RMC-6236 in people with Non-small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC), run by Revolution Medicines, Inc. at 17 sites in United States.
Trial summary
This study is to evaluate the safety and tolerability of RMC-9805 as monotherapy and in combination with RMC-6236 in adults with KRAS G12D-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 Ductal Adenocarcinoma (PDAC)
- What is being tested?
- RMC-9805 and RMC-6236
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 604 participants
- Where
- 17 sitesUnited States
- Study dates
- 7 Sep 2023to 30 Apr 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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
- Pathologically documented, locally advanced or metastatic solid tumor with a KRAS G12D-mutation
- Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage
- ECOG performance status 0 or 1
- Adequate organ function
Who cannot join
- Primary central nervous system (CNS) tumors
- Known or suspected leptomeningeal or active brain metastases or spinal cord compression
- Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication
- Participant was previously treated with an investigational KRAS G12D inhibitor, pan- or multi-RAS inhibitor, or had prior therapy with any direct RAS-targeted therapy (eg, degraders and inhibitors)
- Other inclusion/exclusion criteria may apply.
Trial locations and contacts
17 sites in 1 country. Contact the study team or a site near you to ask about taking part.
17 sites in 1 country
United States17 sites, 17 recruiting
- Recruiting
Johns Hopkins University
Baltimore, Maryland, 21287
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
- Recruiting
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
- Recruiting
The Christ Hospital
Cincinnati, Ohio, 45219
- Recruiting
Sarah Cannon Research Institute at Mary Crowley
Dallas, Texas, 75230
- Recruiting
Duke Cancer Center
Durham, North Carolina, 27710
- Recruiting
NEXT Oncology Virginia
Fairfax, Virginia, 22031
- Recruiting
University of Texas, MD Anderson Cancer Center
Houston, Texas, 77030
- Recruiting
Carolina BioOncology Institute
Huntersville, North Carolina, 28078
- Recruiting
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
- Recruiting
Smilow Cancer Hospital (Yale University)
New Haven, Connecticut, 06511
- Recruiting
NYU Langone
New York, New York, 10016
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
- Recruiting
University of California, Davis Comprehensive Cancer Center
Sacramento, California, 95817
- Recruiting
START
San Antonio, Texas, 78229
- Recruiting
Florida Cancer Specialists
Sarasota, Florida, 34232
- Recruiting
Lee Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: Phase 1/1b, Multicenter, Open-Label, Study of RMC 9805 in Participants With Advanced KRASG 12D-Mutant Solid Tumors
This study is to evaluate the safety and tolerability of RMC-9805 as monotherapy and in combination with RMC-6236 in adults with KRAS G12D-mutant solid tumors.
Read the detailed description
This is an open-label, multicenter, Phase 1/1b study of RMC-9805, a selective and orally bioavailable KRAS G12D(ON) inhibitor, in subjects with KRASG12D-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of two arms: RMC-9805 monotherapy arm and RMC-9805 plus RMC-6236 combination arm. Both arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion.
- Conditions
- Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Advanced Solid Tumors
- Being tested
- RMC-9805, RMC-6236
- Keywords
- KRAS G12D (ON), NSCLC, CRC, PDAC, Non-small Cell Lung Cancer, Lung Cancer, Colorectal Cancer, Colon Cancer, Pancreatic Cancer, Metastatic Cancer, Pancreatic Ductal Adenocarcinoma, Pancreatic Neoplasms, Colorectal Neoplasms, Gastrointestinal Neoplasms, KRAS, Colonic Neoplasms
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Lung Neoplasms, Colonic Neoplasms, Pancreatic Neoplasms, Neoplasm Metastasis, Gastrointestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RMC-9805Drug
Oral Tablets
RMC-6236Drug
Oral Tablets
| Study group | Role | What they receive |
|---|---|---|
| RMC-9805 monotherapy arm | Experimental | Dose exploration and dose expansion Receives: Drug: RMC-9805 |
| RMC-9805 plus RMC-6236 combination arm | Experimental | Dose exploration and dose expansion Receives: Drug: RMC-9805; Drug: RMC-6236 |
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 3 years
Dose Limiting Toxicities
Number of participants with Dose Limiting Toxicities (DLTs)
Measured: 21 days
Secondary outcomes (10)
Maximum Observed Blood Concentration (Cmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Cmax of RMC-6236 in combination with RMC-9805
Cmax
Measured: up to 21 weeks
Time to Reach Maximum Blood Concentration (Tmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Tmax of RMC-6236 in combination with RMC-9805
Tmax
Measured: up to 21 weeks
Area Under Blood Concentration Time Curve (AUC) of RMC-9805 as monotherapy and in combination with RMC-6236, and AUC of RMC-6236 in combination with RMC-9805
AUC
Measured: up to 21 weeks
Ratio of accumulation of RMC-9805 from a single dose to steady state with repeated dosing as monotherapy and in combination with RMC-6236, and ratio of accumulation of RMC-6236 in combination with RMC-9805
accumulation ratio
Measured: up to 21 weeks
Elimination Half-Life (t1/2) of RMC-9805 as monotherapy and in combination with RMC-6236, and t1/2 of RMC-6236 in combination with RMC-9805
t1/2
Measured: up to 21 weeks
Overall Response Rate (ORR)
Assess per RECIST v1.1
Measured: up to 3 years
Duration of Response (DOR)
Assess per RECIST v1.1
Measured: up to 3 years
Disease Control Rate (DCR)
Assess per RECIST v1.1
Measured: up to 3 years
Time to Response (TTR)
Assess per RECIST v1.1
Measured: up to 3 years
Progression-Free Survival (PFS)
Assess per RECIST v1.1
Measured: up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2023
- Study start7 Sep 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion30 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- The monotherapy arm of RMC-9805; the combination arm of RMC-9805 plus RMC-6236
- Masking
- None (open label)
- Enrolment
- 604 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
- NCT06040541
- Sponsor's protocol ID
- RMC-9805-001
- Status last verified
- Jun 2026
- First submitted
- 31 Aug 2023
- Last updated
- 3 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Weller C, Burnett GL, Jiang L, Chakraborty S, Zhang D, Vita NA, Dilly J, Kim E, Maldonato B, Seamon K, Eilerts DF, Milin A, Marquez A, Spradlin J, Helland C, Gould A, Ziv TB, Dinh P, Steele SL, Wang Z, Mu Y, Chugh S, Feng H, Hennessey C, Wang J, Roth J, Rees M, Ronan M, Wolpin BM, Hahn WC, Holderfield M, Wang Z, Koltun ES, Singh M, Gill AL, Smith JAM, Aguirre AJ, Jiang J, Knox JE, Wildes D. A neomorphic protein interface catalyzes covalent inhibition of RASG12D aspartic acid in tumors. Science. 2025 Jul 24;389(6758):eads0239. doi: 10.1126/science.ads0239. Epub 2025 Jul 24.
PubMed 40705880Cregg 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
Study at a glance
From the registry record, last updated by the sponsor on 3 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1/1b, Multicenter, Open-Label, Study of RMC 9805 in Participants With Advanced KRASG 12D-Mutant Solid Tumors
- ClinicalTrials.gov ID
- NCT06040541
- Acronym / sponsor ID
- RMC-9805-001
- Conditions
- Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Advanced Solid Tumors
- Keywords
- KRAS G12D (ON), NSCLC, CRC, PDAC, Non-small Cell Lung Cancer, Lung Cancer, Colorectal Cancer, Colon Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 604 participants (estimated)
- Lead sponsor
- Revolution Medicines, Inc.Industry (pharma, biotech, devices)
- Study start
- 7 Sep 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 30 Apr 2027 (estimated)
- First posted
- 15 Sep 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is to evaluate the safety and tolerability of RMC-9805 as monotherapy and in combination with RMC-6236 in adults with KRAS G12D-mutant solid tumors.
Detailed description
This is an open-label, multicenter, Phase 1/1b study of RMC-9805, a selective and orally bioavailable KRAS G12D(ON) inhibitor, in subjects with KRASG12D-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of two arms: RMC-9805 monotherapy arm and RMC-9805 plus RMC-6236 combination arm. Both arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- The monotherapy arm of RMC-9805; the combination arm of RMC-9805 plus RMC-6236
| Arm | Type | Receives |
|---|---|---|
| RMC-9805 monotherapy arm | Experimental | Drug: RMC-9805Dose exploration and dose expansion |
| RMC-9805 plus RMC-6236 combination arm | Experimental | Drug: RMC-9805, Drug: RMC-6236Dose exploration and dose expansion |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Pathologically documented, locally advanced or metastatic solid tumor with a KRAS G12D-mutation
- Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage
- ECOG performance status 0 or 1
- Adequate organ function
Key exclusion criteria (5 listed)
- Primary central nervous system (CNS) tumors
- Known or suspected leptomeningeal or active brain metastases or spinal cord compression
- Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication
- Participant was previously treated with an investigational KRAS G12D inhibitor, pan- or multi-RAS inhibitor, or had prior therapy with any direct RAS-targeted therapy (eg, degraders and inhibitors)
- Other inclusion/exclusion criteria may apply.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RMC-9805Oral Tablets | Drug | RMC-9805 monotherapy arm, RMC-9805 plus RMC-6236 combination arm |
| RMC-6236Oral Tablets | Drug | RMC-9805 plus RMC-6236 combination arm |
Primary outcome
Adverse events
Time frame: Up to 3 years
Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs, and vital signs
Dose Limiting Toxicities
Time frame: 21 days
Number of participants with Dose Limiting Toxicities (DLTs)
10 secondary outcomes
Maximum Observed Blood Concentration (Cmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Cmax of RMC-6236 in combination with RMC-9805
Time frame: up to 21 weeks
Time to Reach Maximum Blood Concentration (Tmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Tmax of RMC-6236 in combination with RMC-9805
Time frame: up to 21 weeks
Area Under Blood Concentration Time Curve (AUC) of RMC-9805 as monotherapy and in combination with RMC-6236, and AUC of RMC-6236 in combination with RMC-9805
Time frame: up to 21 weeks
Ratio of accumulation of RMC-9805 from a single dose to steady state with repeated dosing as monotherapy and in combination with RMC-6236, and ratio of accumulation of RMC-6236 in combination with RMC-9805
Time frame: up to 21 weeks
Elimination Half-Life (t1/2) of RMC-9805 as monotherapy and in combination with RMC-6236, and t1/2 of RMC-6236 in combination with RMC-9805
Time frame: up to 21 weeks
Overall Response Rate (ORR)
Time frame: up to 3 years
Duration of Response (DOR)
Time frame: up to 3 years
Disease Control Rate (DCR)
Time frame: up to 3 years
Time to Response (TTR)
Time frame: up to 3 years
Progression-Free Survival (PFS)
Time frame: up to 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2026.
- Derived from this study: PubMed 40705880Weller C, Burnett GL, Jiang L, Chakraborty S, Zhang D, Vita NA, Dilly J, Kim E, Maldonato B, Seamon K, Eilerts DF, Milin A, Marquez A, Spradlin J, Helland C, Gould A, Ziv TB, Dinh P, Steele SL, Wang Z, Mu Y, Chugh S, Feng H, Hennessey C, Wang J, Roth J, Rees M, Ronan M, Wolpin BM, Hahn WC, Holderfield M, Wang Z, Koltun ES, Singh M, Gill AL, Smith JAM, Aguirre AJ, Jiang J, Knox JE, Wildes D. A neomorphic protein interface catalyzes covalent inhibition of RASG12D aspartic acid in tumors. Science. 2025 Jul 24;389(6758):eads0239. doi: 10.1126/science.ads0239. Epub 2025 Jul 24.
- Derived from this study: PubMed 40056080Cregg 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Revolution Medicines, Inc. study director
Revolution Medicines, Inc.
17 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing RMC-9805 and RMC-6236 in people with Non-small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC), run by Revolution Medicines, Inc. at 17 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 3 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Revolution Medicines, Inc. (1-844-2-REVMED, medinfo@RevMed.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse events (time frame: Up to 3 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06040541, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Jun 2026.