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Completed

NCT Number: NCT05054725

Combination Study of RMC-4630 and Sotorasib for NSCLC Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies

The purpose of this study is to evaluate the antitumor effects of sotorasib and RMC-4630 in subjects with KRASG12C mutant NSCLC

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Key information

Conditions

Non-small Cell Lung Cancer Bronchial Diseases Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hereditary Sensory and Autonomic Neuropathies Heredodegenerative Disorders, Nervous System Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Nervous System Diseases Nervous System Malformations Neurodegenerative Diseases Neuromuscular Diseases Peripheral Nervous System Diseases Polyneuropathies Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

South West Oncology, Warrnambool, Victoria, Australia

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About this study

This is a phase 2 multicenter, open-label study evaluating the efficacy, safety, tolerability, and pharmacokinetics (PK) of RMC-4630 in combination with sotorasib in subjects with KRASG12C mutant NSCLC after failure of prior standard therapies.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Subject must be ≥18 years of age.
  • Subject must have pathologically documented, locally advanced or metastatic KRASG12C NSCLC (not amenable to curative surgery) that has progressed on prior standard therapies (no more than 3 prior lines of therapies are allowed)

Exclusion criteria

  • Primary central nervous system (CNS) tumors
  • Known or suspected leptomeningeal or brain metastases or spinal cord compression
  • Clinically significant cardiac disease
  • Known impairment of GI function that would alter the absorption
  • Active autoimmune disease requiring systemic treatment within past 2 years
  • History of severe allergic reactions to any of the study intervention components
  • Major surgical procedures within 28 days or non-study-related minor procedures within 7 days of treatment.
  • Prior therapy with KRASG12C inhibitor and/or SHP2 inhibitor

Treatment and study plan

RMC-4630

Drug

RMC-4630 administered orally as a capsule

Other names: SAR442720

Sotorasib

Drug

Sotorasib administered orally as a tablet

Other names: AMG 510, Lumakras

Primary outcomes

  1. Objective Response Rate (ORR) as Assessed Per RECIST v1.1

    Time frame: 31 months

    Evaluation of the antitumor effects of RMC-4630 and sotorasib in locally advanced or metastatic NSCLC patients with KRASG12C mutation with and without co-existing genetic aberrations in specific genes such as STK11/LKB1, KEAP1, and PIK3CA after failure of prior standard therapy. Objective Response Rate (%) is defined as the proportion of patients with Best Overall Response of confirmed CR, or PR. Response was confirmed by a repeat assessment no less than 28 days.

Secondary outcomes

  1. Clinically Significant Changes in Vital Signs

    Time frame: 31 months

    Characterization of the safety, tolerability of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC after failure of prior standard therapy

  2. Clinically Significant Changes in Laboratory Tests

    Time frame: 31 months

    Characterization of the safety, tolerability of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC after failure of prior standard therapy

  3. Clinically Significant Changes in ECGs

    Time frame: 31 months

    Characterization of the safety, tolerability of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC after failure of prior standard therapy

  4. Trough and Approximate Peak Concentrations of RMC-4630

    Time frame: 31 months

    Characterization of PK of RMC-4630 in combination with sotorasib for subjects with KRASG12C mutant NSCLC.

  5. Trough and Approximate Peak Concentrations of Sotorasib

    Time frame: 31 months

    Characterization of PK of RMC-4630 in combination with Sotorasib for subjects with KRASG12C mutant NSCLC

  6. Duration of Response (DOR) as Assessed Per RECIST v1.1

    Time frame: 31 months

    Characterization of efficacy or RMC-4630 in combination with Sotorasib as assessed by DOR, DCR, PFS, and OS in patients with KRAS G12C-mutant locally advanced or metastatic NSCLC after failure of prior standard therapy

  7. Disease Control Rate (DCR) as Assessed Per RECIST v.1.1

    Time frame: 31 months

    Characterization of efficacy or RMC-4630 in combination with Sotorasib as assessed by DOR, DCR, PFS, and OS in patients with KRAS G12C-mutant locally advanced or metastatic NSCLC after failure of prior standard therapy

  8. Progression-free Survival (PFS) as Assessed Per RECIST v1.1

    Time frame: 31 months

    Characterization of efficacy or RMC-4630 in combination with Sotorasib as assessed by DOR, DCR, PFS, and OS in patients with KRAS G12C-mutant locally advanced or metastatic NSCLC after failure of prior standard therapy

  9. Overall Survival (OS)

    Time frame: 31 months

    Characterization of efficacy or RMC-4630 in combination with Sotorasib as assessed by DOR, DCR, PFS, and OS in patients with KRAS G12C-mutant locally advanced or metastatic NSCLC after failure of prior standard therapy

  10. Incidence, Nature and Severity of TEAEs, SAEs

    Time frame: 31 months

    Characterization of the safety, tolerability of RMC-4630 in combination with sotorasib for patients with KRASG12C-mutant NSCLC after failure of prior standard therapy. The specifics of the incidence, nature and severity data can be found under the Adverse Events section.

Sponsors and collaborators

Lead sponsor

Revolution Medicines, Inc.

Industry

Collaborators

  • Amgen
  • Sanofi

Registry information

Official study title

A Phase 2, Open-Label, Multicenter Study of the Combination of RMC-4630 and Sotorasib for Non-Small Cell Lung Cancer Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies

Important dates

Study start
2021
Primary completion
2024
Study completion
2024
First posted
Sep 23, 2021
Registry last updated
Jan 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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