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Non-small Cell Lung Cancer (NSCLC)Phase 1/2NCT05379985

Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS

A Phase 1/2 study testing RMC-6236 in people with Non-small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC), run by Revolution Medicines, Inc. at 21 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

Evaluate the safety and tolerability of RMC-6236 in adults with specific RAS mutant advanced solid tumors. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
RMC-6236
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
754 participants
Where
21 sitesUnited States
Study dates
31 May 2022to 26 Jul 2027
Phase
Phase 1/2
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

  • Histologically confirmed advanced solid tumor with specific KRAS G12 mutations (dose escalation) or RAS mutations (dose optimization/expansion) identified through deoxyribonucleic acid (DNA) sequencing. PDAC with wild-type RAS (expansion).
  • Treatment naive or have received prior standard therapy appropriate for tumor type and stage
  • Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate organ function

Who cannot join

  • Primary central nervous system (CNS) tumors
  • Active, untreated brain metastases
  • Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication
  • History of any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy
  • Other inclusion/exclusion criteria may apply.

Trial locations and contacts

21 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Revolution Medicines, Inc. contact

1-844-273-8633

medinfo@revmed.com

21 sites in 1 country

United States21 sites, 21 recruiting

  • Piedmont Healthcare

    Atlanta, Georgia, 30318

    Recruiting

  • University of Texas at Austin

    Austin, Texas, 78712

    Recruiting

  • Johns Hopkins University

    Baltimore, Maryland, 21287

    Recruiting

  • Mary Bird Perkins Cancer Center

    Baton Rouge, Louisiana, 70809

    Recruiting

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

    Recruiting

  • Tennessee Oncology

    Chattanooga, Tennessee, 37404

    Recruiting

  • Christ Hospital Cancer Center

    Cincinnati, Ohio, 45219

    Recruiting

  • Mary Crowley Cancer Research

    Dallas, Texas, 75230

    Recruiting

  • Next Oncology Virginia

    Fairfax, Virginia, 22031

    Recruiting

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

    Recruiting

  • Taylor Cancer Research Center

    Maumee, Ohio, 43537

    Recruiting

  • Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

    Recruiting

  • Perlmutter Cancer Center at NYU Langone Health

    New York, New York, 10016

    Recruiting

  • Memorial Sloan-Kettering Cancer Center

    New York, New York, 10021

    Recruiting

  • Columbia University

    New York, New York, 10032

    Recruiting

  • UC Irvine/Chao Family Comprehensive Cancer Center

    Orange, California, 92868

    Recruiting

  • Huntsman Cancer Institute

    Salt Lake City, Utah, 84112

    Recruiting

  • Next Oncology

    San Antonio, Texas, 78229

    Recruiting

  • UCLA

    Santa Monica, California, 90404

    Recruiting

  • Virginia Mason Medical Center

    Seattle, Washington, 98101

    Recruiting

  • Moffitt Cancer Center

    Tampa, Florida, 33612

    Recruiting

Other trials in United States

About this study

Official title: A Multicenter Open-Label Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS

Evaluate the safety and tolerability of RMC-6236 in adults with specific RAS mutant advanced solid tumors.

Read the detailed description

This is a Phase 1/2, multicenter open-label study to evaluate the safety, tolerability, pharmacokinetics (PK), and clinical activity of escalating doses of RMC-6236 in adult patients with advanced solid tumors harboring specific RAS mutations, and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose [RP2D] within investigated patient population groups. RMC-6236 is a potent, orally bioavailable RAS-MULTI(ON) inhibitor, selective for the active RAS(ON) form of both wild type and mutant variants of the canonical RAS isoforms (HRAS, NRAS, and KRAS).

Being tested
RMC-6236
Keywords
KRAS, Non-small Cell Lung Cancer, Lung Cancer, Colorectal Cancer, Colon Cancer, Metastatic Cancer, Pancreatic Cancer, Pancreatic Ductal Adenocarcinoma, NSCLC, CRC, PDAC, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Colorectal Neoplasms, Colonic Neoplasms, Intestinal Neoplasms, Gastrointestinal Neoplasms, Lung Neoplasms, Carcinoma, Non-Small-Cell Lung, Neoplastic Processes
Medical subject headings
Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Lung Neoplasms, Colonic Neoplasms, Neoplasm Metastasis, Pancreatic Neoplasms, Carcinoma, Pancreatic Ductal, Intestinal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RMC-6236Drug

    Oral Tablets

Study groups in NCT05379985
Study groupRoleWhat they receive
Experimental: RMC-6236ExperimentalEnrollment into dose exploration may be from any advanced solid tumor type with KRAS p.G12 mutations. Enrollment into dose expansion/optimization may be from groups consisting of patients with a single histotype/genotype (for example, KRAS G12-mutated NSCLC, PDAC, CRC, RAS mutant NSCLC, Melanoma, gynecological cancer or other solid tumors not previously specified). RAS mutant is defined as any nonsynonymous mutation of KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61)
Receives: Drug: RMC-6236

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs, including incidence and severity of findings in laboratory values and vital signs

    Measured: up to 2.5 years

  2. Number of Participants with Dose-Limiting Toxicity (DLT)

    Measured: 21 days

Secondary outcomes (10)

  1. Maximum Observed Blood Concentration (Cmax) of RMC-6236

    Measured: up to 15 weeks

  2. Time to Reach Maximum Blood Concentration (Tmax) of RMC-6236

    Measured: up to 15 weeks

  3. Area Under Blood Concentration Time Curve (AUC) of RMC-6236

    Measured: up to 15 weeks

  4. Elimination Half-Life of RMC-6236 (t1/2)

    Measured: up to 15 weeks

  5. Ratio of accumulation of RMC-6236 from a single dose to steady state with repeated dosing

    Measured: up to 15 weeks

  6. Overall Response Rate (ORR)

    Overall response rate per RECIST v1.1

    Measured: up to 2.5 years

  7. Duration of Response (DOR)

    Duration of response per RECIST v1.1

    Measured: up to 2.5 years

  8. Disease Control Rate (DCR)

    Disease control rate per RECIST v1.1

    Measured: up to 2.5 years

  9. Time to Response (TTR)

    Time to response per RECIST v1.1

    Measured: up to 2.5 years

  10. Progression-Free Survival (PFS)

    Progression-free survival per RECIST v1.1

    Measured: up to 2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2022
  2. Study start31 May 2022
  3. Primary completion31 May 2027 (estimated)
  4. Study completion26 Jul 2027 (estimated)

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
754 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05379985
Sponsor's protocol ID
RMC-6236-001
Status last verified
May 2026
First submitted
13 May 2022
Last updated
15 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Arbour KC, Punekar S, Luo J, Johnson M, Spira A, Herzberg B, Starodub A, Sommerhalder D, Hecht JR, Garrido-Laguna I, Barve M, Ou SI, Kar S, Bao L, Tao L, Vora R, Hegde A, Saltos A, Azad NS, Hong DS; RMC-6236-001 Investigators. Daraxonrasib for Previously Treated RAS-Mutant Non-Small-Cell Lung Cancer. N Engl J Med. 2026 Sep 3;395(9):882-893. doi: 10.1056/NEJMoa2504059.

    PubMed 42685317

  • Wolpin BM, Park W, Garrido-Laguna I, Spira A, Starodub A, Sommerhalder D, Punekar SR, Barve M, Pelster M, Herzberg B, Azad NS, Hecht JR, Ou SHI, Lin T, Kar S, Tao L, Vora R, Hegde A, Aung K, Hong DS; RMC-6236-001 Investigators. Daraxonrasib in Previously Treated Advanced RAS-Mutated Pancreatic Cancer. N Engl J Med. 2026 May 7;394(18):1790-1802. doi: 10.1056/NEJMoa2505783.

    PubMed 42090791

  • Jiang J, Jiang L, Maldonato BJ, Wang Y, Holderfield M, Aronchik I, Winters IP, Salman Z, Blaj C, Menard M, Brodbeck J, Chen Z, Wei X, Rosen MJ, Gindin Y, Lee BJ, Evans JW, Chang S, Wang Z, Seamon KJ, Parsons D, Cregg J, Marquez A, Tomlinson ACA, Yano JK, Knox JE, Quintana E, Aguirre AJ, Arbour KC, Reed A, Gustafson WC, Gill AL, Koltun ES, Wildes D, Smith JAM, Wang Z, Singh M. Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers. Cancer Discov. 2024 Jun 3;14(6):994-1017. doi: 10.1158/2159-8290.CD-24-0027.

    PubMed 38593348

  • Holderfield M, Lee BJ, Jiang J, Tomlinson A, Seamon KJ, Mira A, Patrucco E, Goodhart G, Dilly J, Gindin Y, Dinglasan N, Wang Y, Lai LP, Cai S, Jiang L, Nasholm N, Shifrin N, Blaj C, Shah H, Evans JW, Montazer N, Lai O, Shi J, Ahler E, Quintana E, Chang S, Salvador A, Marquez A, Cregg J, Liu Y, Milin A, Chen A, Ziv TB, Parsons D, Knox JE, Klomp JE, Roth J, Rees M, Ronan M, Cuevas-Navarro A, Hu F, Lito P, Santamaria D, Aguirre AJ, Waters AM, Der CJ, Ambrogio C, Wang Z, Gill AL, Koltun ES, Smith JAM, Wildes D, Singh M. Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy. Nature. 2024 May;629(8013):919-926. doi: 10.1038/s41586-024-07205-6. Epub 2024 Apr 8.

    PubMed 38589574

  • Schulze CJ, Seamon KJ, Zhao Y, Yang YC, Cregg J, Kim D, Tomlinson A, Choy TJ, Wang Z, Sang B, Pourfarjam Y, Lucas J, Cuevas-Navarro A, Ayala-Santos C, Vides A, Li C, Marquez A, Zhong M, Vemulapalli V, Weller C, Gould A, Whalen DM, Salvador A, Milin A, Saldajeno-Concar M, Dinglasan N, Chen A, Evans J, Knox JE, Koltun ES, Singh M, Nichols R, Wildes D, Gill AL, Smith JAM, Lito P. Chemical remodeling of a cellular chaperone to target the active state of mutant KRAS. Science. 2023 Aug 18;381(6659):794-799. doi: 10.1126/science.adg9652. Epub 2023 Aug 17.

    PubMed 37590355

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing RMC-6236 in people with Non-small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC), run by Revolution Medicines, Inc. at 21 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 15 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 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 combined 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.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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. (1-844-273-8633, medinfo@revmed.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs, including incidence and severity of findings in laboratory values and vital signs (time frame: up to 2.5 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 NCT05379985, which also lists 5 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 15 May 2026.

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