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Non-Small Cell Lung Cancer (NSCLC)Phase 1NCT05462717

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

A Phase 1 study testing RMC-6291 in people with Non-Small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC), run by Revolution Medicines, Inc. at 64 sites in 13 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
RMC-6291
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
222 participants
Where
64 sitesin 13 countries
Study dates
19 Sep 2022to 30 Sep 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

  • 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

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.
  • Prior therapy with KRASG12C (ON) inhibitor
  • Other inclusion/exclusion criteria may apply.

Trial locations and contacts

64 sites in 13 countries.

64 sites in 13 countries

United States15 sites

  • American Oncology Partners of Maryland

    Bethesda, Maryland, 20817

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Comprehensive Cancer Center

    Buffalo, New York, 14203

  • Next Oncology Virginia

    Fairfax, Virginia, 22031

  • University of Miami School of Medicine Sylvester Comprehensive Cancer Center

    Miami, Florida, 33136

  • Tennessee Oncology

    Nashville, Tennessee, 37203

  • MSK Cancer Center

    New York, New York, 10021

  • Columbia University Irving Medical Center

    New York, New York, 10032

  • UC Irvine Cancer Center

    Orange, California, 92868

  • UC Davis Cancer Center

    Sacramento, California, 95817

  • Next Oncology

    San Antonio, Texas, 78229

  • START

    San Antonio, Texas, 78229

  • UCSF

    San Francisco, California, 94158

  • Highlands Oncology Group

    Springdale, Arkansas, 72762

  • Moffitt Cancer Center

    Tampa, Florida, 33612

Other trials in United States

Spain9 sites

  • NEXT Oncology IOB Hospital Quirónsalud

    Barcelona, 08023

  • ICO Hospitalet

    Barcelona, 08908

  • Clínica Universidad de Navarra

    Madrid, 28027

  • MD Anderson Cancer Center

    Madrid, 28033

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid, 28040

  • Clinica Universidad de Navarra

    Pamplona, 31008

  • Hospital Universitario Quirónsalud

    Pozuelo de Alarcón, 28223

  • Hospital Universitario Virgen del Rocío

    Seville, 41013

  • Hospital Universitario Miguel Servet

    Zaragoza, 50009

Other trials in Spain

France7 sites

  • ICO

    Angers, 49055

  • CHU Bordeaux Hospital Saint-Andre

    Bordeaux, 33000

  • Centre Jean Perrin

    Clermont-Ferrand, 63011

  • Centre Oscar Lambret

    Lille, 59000

  • Centre Léon Bérard

    Lyon, 69008

  • CHU Nantes

    Nantes, 44093

  • ICANS

    Strasbourg, 67200

Other trials in France

Italy6 sites

  • S.C. Oncologia Falck, Dipartimento Ematologia ed Oncologia Niguarda Cancer Center

    Milan, 20162

  • Istituto Europeo Oncologico

    Milan, 20141

  • Istituto Nazionale Tumori Fondazione G. Pascale

    Naples, 80131

  • Azienda Ospedaliero-Universitaria San Luigi Gonzaga

    Orbassano, 10043

  • Fondazione IRCCS Policlinico San Matteo

    Pavia, 27100

  • Centro Ricerche Cliniche di Verona s.r.l.

    Verona, 37134

Other trials in Italy

Australia4 sites

  • Peninsula & South Eastern Haematology and Oncology Group

    Frankston, Victoria, 3199

  • Austin Health, Olivia Newton-John Cancer Research & Wellness Centre

    Heidelberg, Victoria, 3084

  • Southside Cancer Care Centre

    Sydney, New South Wales, 2228

  • South West Health Care

    Warrnambool, Victoria, 3280

Other trials in Australia

South Korea4 sites

  • Korea University Hospital

    Seoul, 02708

  • Seoul National University Hospital

    Seoul, 3080

  • Severance Hospital

    Seoul, 3722

  • Ajou University Hospital

    Suwon, Gyeonggi-do, 16499

Other trials in South Korea

Taiwan4 sites

  • E-DA hospital

    Kaohsiung City, Yanchao District, 82445

  • Taipei Tzu Chi Hospital

    New Taipei City, 231

  • National Cheng Kung University Hospital

    Tainan, 70457

  • National Taiwan University Hospital

    Taipei, 10048

Other trials in Taiwan

Czechia3 sites

  • NH Hospital a.s.

    Hořovice, 268 31

  • Klinika onkologie a radioterapie, Fakultni Nemocnice Hradec Kralove

    Hradec Králové, 50005

  • Onkologicka klinika, Fakultni Nemocnice Olomouc

    Olomouc, 77900

Other trials in Czechia

Poland3 sites

  • Instytut MSF Sp zoo

    Lodz, 90-302

  • Med - Polonia Sp. z o. o.

    Poznan, 60-693

  • Narodowy Instytut Onkologii

    Warsaw, 02-781

Other trials in Poland

Serbia3 sites

  • MSB General Hospital

    Belgrade, 11000

  • Clinical hospital center Bezanijska Kosa

    Belgrade, 11071

  • Institute for pulmonary diseases Sremska Kamenica

    Kamenitz, 21204

Other trials in Serbia

Thailand3 sites

  • Siriraj Hospital

    Bangkok Noi, 10700

  • Chiang Mai University

    Chiang Mai, 50200

  • Khon Kaen University

    Khon Kaen, 40002

Other trials in Thailand

Malaysia2 sites

  • University Malaya Medical Centre

    Kuala Lumpur, 59100

  • Sarawak General Hospital

    Kuching, 93586

Other trials in Malaysia

Singapore1 site

  • National Cancer centre Singapore

    Singapore, 168583

Other trials in Singapore

About this study

Official title: 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.

Read the 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.

Being tested
RMC-6291
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.

  • RMC-6291Drug

    Oral tablet once or twice a day

Study groups in NCT05462717
Study groupRoleWhat they receive
RMC-6291ExperimentalDose Escalation and Dose Expansion
Receives: Drug: RMC-6291

What is being measured

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

  1. Adverse events

    Number of participants with adverse events

    Measured: up to 3 years

  2. Dose Limiting Toxicities

    Number of participants with dose limiting toxicities

    Measured: The first 21 days (i.e. Cycle 1)

Secondary outcomes (10)

  1. Maximum Observed Blood Concentration of RMC-6291

    Cmax

    Measured: 7 Cycles

  2. Time to Reach Maximum Blood Concentration of RMC-6291

    Tmax

    Measured: 7 Cycles

  3. Area Under Blood Concentration Time Curve of RMC-6291

    AUC

    Measured: 7 Cycles

  4. Elimination Half-Life of RMC-6291

    t1/2

    Measured: 7 Cycles

  5. Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing

    accumulation ratio

    Measured: 7 Cycles

  6. Overall Response Rate (ORR)

    Overall response rate per RECIST v1.1

    Measured: 3 years

  7. Duration of Response (DOR)

    Duration of response per RECIST v1.1

    Measured: 3 years

  8. Disease Control Rate (DCR)

    Disease control rate per RECIST v1.1

    Measured: 3 years

  9. Time to Response (TTR)

    Time to response per RECIST v1.1

    Measured: 3 years

  10. Progression-Free Survival (PFS)

    Progression-free survival per RECIST v1.1

    Measured: 3 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 Jul 2022
  2. Study start19 Sep 2022
  3. Primary completion31 Mar 2027 (estimated)
  4. Study completion30 Sep 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
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
222 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05462717
Sponsor's protocol ID
RMC-6291-001
Status last verified
May 2026
First submitted
11 Jul 2022
Last updated
15 May 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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 study testing RMC-6291 in people with Non-Small Cell Lung Cancer (NSCLC) and Colorectal Cancer (CRC), run by Revolution Medicines, Inc. at 64 sites in 13 countries.

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 5 inclusion and 6 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: under way, not looking for participants, 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 64 sites in United States, Spain, France, Italy, Australia and 8 more countries. 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. 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 NCT05462717, which also lists 1 linked publication.

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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