Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors

NCT07349537
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Phase
Phase 1
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Recruitment status
Recruiting
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Participants
574
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Lead sponsor
Revolution Medicines, Inc.
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Start date
2026-01-08
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Number of sites
9
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Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RMC-5127 as a monotherapy and in combination with either daraxonrasib or cetuximab in adults with KRAS G12V-mutant solid tumors.
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Short title
Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors
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Official title
Phase 1/1b, Multicenter, Open-Label, Study of RMC-5127 in Patients With Advanced KRAS G12V-Mutant Solid Tumors
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2028-10-01
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First posted
2026-01-16
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Registry last updated
2026-07-10
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Primary completion date
2028-04-01
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Start date
2026-01-08
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Participants
574
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Participant count basis
Estimated
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Planned participants
574
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Protocol amendments
0
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Number of sites
9
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Revolution Medicines, Inc.
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Source registry
ClinicalTrials.gov
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Registry ID
NCT07349537
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ClinicalTrials.gov ID
NCT07349537
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Registry record
Open registry record
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Allocation
Not randomised
Model
Parallel groups
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

  1. Number of patients with adverse events (AEs)

    Timeframe: Up to approximately 3 years

    Number of patients with AEs as assessed by Common Terminology Criteria for Adverse Events CTCAE v5

  2. Changes in vital signs

    Timeframe: Up to approximately 3 years

    Number of patients with changes from baseline in vital signs

  3. Changes in electrocardiogram (ECG) test values

    Timeframe: Up to approximately 3 years

    Number of patients with changes from baseline in ECG test values

  4. Changes in clinical laboratory test values

    Timeframe: Up to approximately 3 years

    Number of patients with changes from baseline in clinical laboratory test values

  5. Dose Limiting Toxicities

    Timeframe: Up to 28 days

    Number of patients with dose limiting toxicities

  1. Cmax concentrations of RMC-5127 and daraxonrasib

    Timeframe: Up to Cycle 5 Day 1 (each cycle is up to 28 days)

    Maximum blood concentration (Cmax) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and Cmax of daraxonrasib in combination with RMC-5127 over time as applicable

  2. Tmax concentration of RMC-5127 and daraxonrasib

    Timeframe: Up to Cycle 5 Day 1 (each cycle is up to 28 days)

    Time to reach maximum blood concentration (Tmax) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and Tmax of daraxonrasib in combination with RMC-5127 over time as applicable

  3. AUC concentrations of RMC-5127 and daraxonrasib

    Timeframe: Up to Cycle 5 Day 1 (each cycle is up to 28 days)

    Area under the blood concentration time curve (AUC) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and AUC of daraxonrasib in combination with RMC-5127 over time as applicable

  4. Ratio of accumulation of RMC-5127

    Timeframe: Up to Cycle 5 Day 1 (each cycle is up to 28 days)

    Ratio of accumulation of RMC-5127 from a single dose to steady state with repeated dosing as monotherapy and in combination with darabxrasib or cetuximab over time as applicable

  5. Half-Life of RMC-5127 and daraxonrasib

    Timeframe: Up to Cycle 5 Day 1 (each cycle is up to 28 days)

    Elimination Half-Life (t1/2) of RMC-5127 as monotherapy and in combination with daraxonrasib or cetuximab, and t1/2 of daraxonrasib in combination with RMC-5127 over time as applicable

  6. Objective Response Rate (ORR)

    Timeframe: Up to approximately 3 years

    ORR per response evaluation criteria in solid tumors (RECIST) v1.1

  7. Duration of Response (DOR)

    Timeframe: Up to approximately 3 years

    DOR per RECIST v1.1

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • At least 18 years old and has provided informed consent.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  • Pathologically documented, locally advanced or metastatic KRAS G12V-mutated solid tumor malignancy.
  • Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage.
  • Measurable per RECIST v1.1
  • Adequate organ function (bone marrow, liver, kidney, coagulation).
  • Able to take oral medications.

  • Primary central nervous system (CNS) tumors
  • Prior therapy with KRAS G12V inhibitor or direct RAS-targeted therapy (eg. degraders and/or inhibitors).
  • Any conditions that may affect the ability to take or absorb study drug.
  • Major surgery within 28 days prior to receiving study drug(s).
  • Patient is unable or unwilling to comply with protocol-required study visits or procedures.
Sources for eligibility
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  • Yale Cancer CenterNew Haven, United StatesRecruiting
  • Johns HopkinsBaltimore, United StatesRecruiting
  • Dana-Farber Cancer InstituteBoston, United StatesRecruiting
  • START MidwestGrand Rapids, United StatesRecruiting
  • Laura and Isaac Perlmutter Cancer Center at NYU Langone HealthNew York, United StatesRecruiting
  • NEXT - DallasDallas, United StatesRecruiting
  • NEXTSan Antonio, United StatesRecruiting
  • START - San AntonioSan Antonio, United StatesRecruiting
  • NEXT - VirginiaFairfax, United StatesRecruiting
Sources for sites
clinicaltrials.gov

Related records

Drugs (1)

Lead sponsors (1)

Conditions (9)

Targets (1)