Testing the Use of Targeted Treatment (AMG 510) for KRAS G12C Mutated Advanced Non-squamous Non-small Cell Lung Cancer (A Lung-MAP Treatment Trial)

Summary

Objectives

PRIMARY OBJECTIVE:
I. To evaluate the response rate (confirmed, complete or partial) of sotorasib (AMG 510) in participants with KRAS^G12C mutated stage IV or recurrent non-squamous non-small cell lung cancer (NSCLC).

SECONDARY OBJECTIVES:
I. To evaluate investigator assessed progression-free survival (IA-PFS) within each cohort.
II. To evaluate overall survival (OS) within each cohort.
III. To evaluate duration of response (DOR) among responders within each cohort.
IV. To evaluate the frequency and severity of toxicities within the full study population (all cohorts combined).

TRANSLATIONAL MEDICINE OBJECTIVES:
I. To evaluate the association between clinical outcomes (response, IA-PFS, OS) and other co-mutations (e.g., CDKN2A/B/C, ATM, PIK3CA) identified by the Foundation Medicine Inc (FMI) FoundationOne CDx from LUNGMAP, within cohorts and across the full study population of KRAS^G12C positive participants.
II. To evaluate the association between clinical outcomes (response, IA-PFS, OS) and PD-L1 total proportion score determined by screening in LUNGMAP, within cohorts and across the full study population of KRAS^G12C positive participants.
III. To evaluate the association between clinical outcomes (response, IA-PFS, OS) and Tumor Mutational Burden Score determined by the FMI FoundationOne CDx from LUNGMAP, within cohorts and across the full study population of KRAS^G12C positive participants.
IV. To collect, process, and bank cell-free deoxyribonucleic acid (cfDNA) at pre-treatment on cycle 1 day 1, cycle 2 day 1, cycle 3 day 1, and at progression for future development of a proposal to evaluate comprehensive next-generation sequencing of circulating tumor DNA (ctDNA) and association with clinical outcomes.
Note: The translational medicine proposal to use these specimens will be submitted as a revision to CTEP for approval, prior to the SWOG Statistical and Data Management Center (SDMC) review of assay results.
V. To establish a tissue/blood repository from participants with refractory NSCLC.

OUTLINE:
Patients receive sotorasib orally (PO) once daily (QD) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 3 years if the disease has not gotten worse at the time of finishing study treatment. If the disease has gotten worse, patients are followed up every 6 months for 2 years, then at the end of the 3 years from the time they go on study.