2022 World Conference on Lung Cancer (ePosters)-EP08.02-111. RMC-4630, a SHP2 Inhibitor, in Combination with Sotorasib for Advanced KRASG12C NSCLC After Failure of Prior Standard Therapies: A Phase 2 Trial

EP08.02-111. RMC-4630, a SHP2 Inhibitor, in Combination with Sotorasib for Advanced KRASG12C NSCLC After Failure of Prior Standard Therapies: A Phase 2 Trial

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The document describes a Phase 2 clinical trial (RMC-4630-03) for the treatment of advanced non-small cell lung cancer (NSCLC) with a specific mutation called KRASG12C. The trial aims to evaluate the combination of RMC-4630, a SHP2 inhibitor, and sotorasib, a KRASG12C inhibitor, in patients who have progressed on prior standard therapies.<br /><br />The trial consists of two phases. The Safety Run-in Phase will enroll up to 6 patients at a lower dose of RMC-4630, with dose escalation guided by a modified toxicity algorithm. The Expansion Phase will enroll up to 40 patients in two different cohorts: Cohort 1 with patients who have KRASG12C mutant NSCLC without specific co-mutations, and Cohort 2 with patients who have KRASG12C mutant NSCLC with co-mutation(s).<br /><br />The rationale for combining RMC-4630 and sotorasib is based on preclinical studies that showed improved anti-tumor activity when SHP2 inhibitors were added to KRASG12C inhibitors. Previous Phase 1 data for RMC-4630 demonstrated anti-tumor activity and tolerability consistent with inhibiting the RAS pathway.<br /><br />The trial has specific inclusion and exclusion criteria, including patients with KRASG12C NSCLC that has progressed on prior therapies and the absence of certain contraindications such as central nervous system tumors and significant cardiac disease. Genomic reports can be used for eligibility confirmation.<br /><br />The objectives of the trial include evaluating the safety, tolerability, and pharmacokinetics of the combination therapy, as well as assessing its efficacy based on parameters such as duration of response, disease control rate, progression-free survival, and overall survival.<br /><br />The trial is jointly funded by Revolution Medicines, Inc. and Sanofi, with Amgen supplying sotorasib. The document acknowledges the participation of patients, caregivers, and clinical trial staff in the trial.<br /><br />Overall, the document provides an overview of the RMC-4630-03 trial, its rationale, objectives, and study design, highlighting the potential of combining RMC-4630 and sotorasib for the treatment of advanced KRASG12C mutant NSCLC.

Asset Subtitle

Melissa L Johnson

Meta Tag

Speaker Melissa L Johnson

Topic Metastatic Non-small Cell Lung Cancer - Molecular Targeted Treatments

Keywords

Phase 2 clinical trial

RMC-4630-03

advanced non-small cell lung cancer

NSCLC

KRASG12C mutation

SHP2 inhibitor

sotorasib

combination therapy

safety run-in phase

expansion phase