Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors

May 12, 2026 updated by: Revolution Medicines, Inc.

Phase 1/1b, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating doses of RMC-6291 (KRAS G12C(ON) inhibitor) monotherapy in adult subjects with advanced solid tumors and to identify the maximum tolerated dose (MTD), and the recommended Phase 2 dose.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is an open-label, multicenter, Phase 1/1b study of RMC-6291 monotherapy in subjects with advanced KRASG12C-mutant solid tumors. The study will include 2 components: a Dose-Escalation and a Dose-Expansion. Subjects will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
222

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Australia
    • New South Wales
      • Sydney, New South Wales, Australia, 2228
        • Southside Cancer Care Centre
    • Victoria
      • Frankston, Victoria, Australia, 3199
        • Peninsula & South Eastern Haematology and Oncology Group
      • Heidelberg, Victoria, Australia, 3084
        • Austin Health, Olivia Newton-John Cancer Research & Wellness Centre
      • Warrnambool, Victoria, Australia, 3280
        • South West Health Care
  • Czechia
      • Hořovice, Czechia, 268 31
        • NH Hospital a.s.
      • Hradec Králové, Czechia, 50005
        • Klinika onkologie a radioterapie, Fakultni Nemocnice Hradec Kralove
      • Olomouc, Czechia, 77900
        • Onkologicka klinika, Fakultni Nemocnice Olomouc
  • France
      • Angers, France, 49055
        • ICO
      • Bordeaux, France, 33000
        • CHU Bordeaux Hospital Saint-Andre
      • Clermont-Ferrand, France, 63011
        • Centre Jean Perrin
      • Lille, France, 59000
        • Centre Oscar Lambret
      • Lyon, France, 69008
        • Centre Léon Bérard
      • Nantes, France, 44093
        • CHU Nantes
      • Strasbourg, France, 67200
        • ICANS
  • Italy
      • Milan, Italy, 20162
        • S.C. Oncologia Falck, Dipartimento Ematologia ed Oncologia Niguarda Cancer Center
      • Milan, Italy, 20141
        • Istituto Europeo Oncologico
      • Naples, Italy, 80131
        • Istituto Nazionale Tumori Fondazione G. Pascale
      • Orbassano, Italy, 10043
        • Azienda Ospedaliero-Universitaria San Luigi Gonzaga
      • Pavia, Italy, 27100
        • Fondazione IRCCS Policlinico San Matteo
      • Verona, Italy, 37134
        • Centro Ricerche Cliniche di Verona s.r.l.
  • Malaysia
      • Kuala Lumpur, Malaysia, 59100
        • University Malaya Medical Centre
      • Kuching, Malaysia, 93586
        • Sarawak General Hospital
  • Poland
      • Lodz, Poland, 90-302
        • Instytut MSF Sp zoo
      • Poznan, Poland, 60-693
        • Med - Polonia Sp. z o. o.
      • Warsaw, Poland, 02-781
        • Narodowy Instytut Onkologii
  • Serbia
      • Belgrade, Serbia, 11000
        • MSB General Hospital
      • Belgrade, Serbia, 11071
        • Clinical Hospital Center Bezanijska Kosa
      • Kamenitz, Serbia, 21204
        • Institute for pulmonary diseases Sremska Kamenica
  • Singapore
      • Singapore, Singapore, 168583
        • National Cancer Centre Singapore
  • South Korea
      • Seoul, South Korea, 3080
        • Seoul National University Hospital
      • Seoul, South Korea, 3722
        • Severance Hospital
      • Seoul, South Korea, 02708
        • Korea University Hospital
    • Gyeonggi-do
      • Suwon, Gyeonggi-do, South Korea, 16499
        • Ajou University Hospital
  • Spain
      • Barcelona, Spain, 08908
        • ICO Hospitalet
      • Barcelona, Spain, 08023
        • NEXT Oncology IOB Hospital Quirónsalud
      • Madrid, Spain, 28040
        • Hospital Universitario Fundación Jiménez Díaz
      • Madrid, Spain, 28027
        • Clinica Universidad de Navarra
      • Madrid, Spain, 28033
        • MD Anderson Cancer Center
      • Pamplona, Spain, 31008
        • Clinica Universidad de Navarra
      • Pozuelo de Alarcón, Spain, 28223
        • Hospital Universitario QuironSalud
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocío
      • Zaragoza, Spain, 50009
        • Hospital Universitario Miguel Servet
  • Taiwan
      • New Taipei City, Taiwan, 231
        • Taipei Tzu Chi Hospital
      • Tainan, Taiwan, 70457
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 10048
        • National Taiwan University Hospital
    • Yanchao District
      • Kaohsiung City, Yanchao District, Taiwan, 82445
        • E-Da Hospital
  • Thailand
      • Bangkok Noi, Thailand, 10700
        • Siriraj Hospital
      • Chiang Mai, Thailand, 50200
        • Chiang Mai University
      • Khon Kaen, Thailand, 40002
        • Khon Kaen University
  • United States
    • Arkansas
      • Springdale, Arkansas, United States, 72762
        • Highlands Oncology Group
    • California
      • Orange, California, United States, 92868
        • UC Irvine Cancer Center
      • Sacramento, California, United States, 95817
        • UC Davis Cancer Center
      • San Francisco, California, United States, 94158
        • UCSF
    • Florida
      • Miami, Florida, United States, 33136
        • University of Miami School of Medicine Sylvester Comprehensive Cancer Center
      • Tampa, Florida, United States, 33612
        • Moffitt Cancer Center
    • Maryland
      • Bethesda, Maryland, United States, 20817
        • American Oncology Partners of Maryland
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
    • New York
      • Buffalo, New York, United States, 14203
        • Roswell Park Comprehensive Cancer Center
      • New York, New York, United States, 10032
        • Columbia University Irving Medical Center
      • New York, New York, United States, 10021
        • MSK Cancer Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Tennessee Oncology
    • Texas
      • San Antonio, Texas, United States, 78229
        • NEXT Oncology
      • San Antonio, Texas, United States, 78229
        • START
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • NEXT Oncology Virginia

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Subject must be ≥18 years of age.
  • Subject must have pathologically documented, locally advanced or metastatic KRASG12C-mutated solid tumor malignancy (not amenable to curative surgery) that has previously been treated with standard-of-care therapies for respective tumor types, is intolerant to, or is considered ineligible for standard-of-care anticancer treatments.
  • ECOG performance status 0 or 1
  • Prior treatment with a KRASG12C (OFF) inhibitor allowed for dose escalation and for NSCLC in dose expansion
  • Adequate organ function

Exclusion Criteria:

  • 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.
  • Prior therapy with KRASG12C (ON) inhibitor

Other inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: RMC-6291
Dose Escalation and Dose Expansion
Drug: RMC-6291
Oral tablet once or twice a day

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Adverse events
Time Frame: up to 3 years
Number of participants with adverse events
up to 3 years
Dose Limiting Toxicities
Time Frame: The first 21 days (i.e. Cycle 1)
Number of participants with dose limiting toxicities
The first 21 days (i.e. Cycle 1)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Maximum Observed Blood Concentration of RMC-6291
Time Frame: 7 Cycles
Cmax
7 Cycles
Time to Reach Maximum Blood Concentration of RMC-6291
Time Frame: 7 Cycles
Tmax
7 Cycles
Area Under Blood Concentration Time Curve of RMC-6291
Time Frame: 7 Cycles
AUC
7 Cycles
Elimination Half-Life of RMC-6291
Time Frame: 7 Cycles
t1/2
7 Cycles
Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing
Time Frame: 7 Cycles
accumulation ratio
7 Cycles
Overall Response Rate (ORR)
Time Frame: 3 years
Overall response rate per RECIST v1.1
3 years
Duration of Response (DOR)
Time Frame: 3 years
Duration of response per RECIST v1.1
3 years
Disease Control Rate (DCR)
Time Frame: 3 years
Disease control rate per RECIST v1.1
3 years
Time to Response (TTR)
Time Frame: 3 years
Time to response per RECIST v1.1
3 years
Progression-Free Survival (PFS)
Time Frame: 3 years
Progression-free survival per RECIST v1.1
3 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Revolution Medicines, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Revolution Medicines, Inc., Revolution Medicines, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 19, 2022

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 30, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 11, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 13, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 18, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 15, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • RMC-6291-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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