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

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

Detailed Description
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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.

Official Title
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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

Conditions
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Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: RMC-4630
* Drug: Sotorasib


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RMC-4630 and sotorasib, Safety Run-in<br>Safety Run-In: RMC-4630 and sotorasib | Drug: RMC-4630<br>* RMC-4630 administered orally as a capsule<br>* Other names: SAR442720;Drug: Sotorasib<br>* Sotorasib administered orally as a tablet<br>* Other names: Lumakras;|
| Experimental: RMC-4630 and sotorasib, Expansion<br>Dose Expansion: RMC-4630 and sotorasib | Drug: RMC-4630<br>* RMC-4630 administered orally as a capsule<br>* Other names: SAR442720;Drug: Sotorasib<br>* Sotorasib administered orally as a tablet<br>* Other names: Lumakras;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | ORR as assessed per RECIST v1.1 | approximately 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of Participants with Adverse Events | approximately 12 months | 
| Serious Adverse Events | Number of Participants with Serious Adverse Events | approximately 12 months | 
| Vital signs | Number of subjects with clinically significant changes in vital signs | approximately 12 months | 
| Clinical laboratory test values | Number of subjects with clinically significant changes in clinical laboratory test values | approximately 12 months | 
| ECGs Measurements | Number of subjects with clinically significant changes in ECGs Measurements | approximately 12 months | 
| Concentration of RMC-4630 | Trough Concentration of RMC-4630 | approximately 12 months | 
| Concentration of sotorasib | Trough Concentration of sotorasib | approximately 12 months | 
| Duration of response (DOR) | DOR as assessed by RECIST v1.1 | approximately 12 months | 
| Disease Control Rate (DCR) | DCR as assessed by RECIST v1.1 | approximately 12 months | 
| Progression-free survival (PFS) | PFS as assessed by RECIST v1.1 | approximately 12 months | 
| Overall survival (OS) | Overall survival (OS) | approximately 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SHP2, NSCLC, KRAS G12C, BRAF Class 1/2/unclassified, KRAS amplification, KRAS mutation, STK11/LKB1, KEAP1, PIK3CA, ATRX, BRCA2, carcinoma, non-small lung cancer, bronchial neoplasms, lung neoplasms, respiratory tract neoplasms, neoplasms by site, neoplasms, lung diseases, respiratory tract diseases