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

April 18, 2024 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

Recruiting

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Estimated)

222

Phase

  • 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 Locations

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

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
  • 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
Intervention / Treatment
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

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

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

Revolution Medicines, Inc.

Investigators

  • Study Director: Revolution Medicines, Inc., Revolution Medicines, Inc.

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)

September 19, 2022

Primary Completion (Estimated)

November 1, 2024

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

July 11, 2022

First Submitted That Met QC Criteria

July 13, 2022

First Posted (Actual)

July 18, 2022

Study Record Updates

Last Update Posted (Actual)

April 19, 2024

Last Update Submitted That Met QC Criteria

April 18, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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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