A Phase 2 interventional study of Sotorasib in Lung Adenocarcinoma, Lung Non-Small Cell Carcinoma and Recurrent Lung Non-Squamous Non-Small Cell Carcinoma, sponsored by SWOG Cancer Research Network. Active, not recruiting at 829 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-12-05.
Sponsored by SWOG Cancer Research Network · Phase 2, Interventional, and Treatment
This phase II Lung-MAP treatment trial studies the effect of AMG 510 in treating non-squamous non-small cell lung cancer that is stage IV or has come back (recurrent) and has a specific mutation in the KRAS gene, known as KRAS G12C. Mutations in this gene may cause the cancer to grow. AMG 510, a targeted treatment against the KRAS G12C mutation, may help stop the growth of tumor cells.
PRIMARY OBJECTIVE:
I. To evaluate the response rate (confirmed, complete or partial) of 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.
OUTLINE:
Patients receive AMG 510 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.
Participants must be informed of the investigational nature of this study and must sign and give informed consent in accordance with institutional and federal guidelines
Exclusion Criteria:
Patients receive AMG 510 PO QD on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Drug: Sotorasib
Given PO
Also known as: AMG 510, AMG-510, AMG510
Response rate (confirmed, complete or partial)
Time frame: Up to 3 years
Incidence of adverse events
The frequency and grade of individual toxicities attributable to treatment will be estimated.
Time frame: Up to 3 years
Progression free survival
Will be estimated using the method of Kaplan-Meier. Confidence intervals about medians will be estimated using the Brookmeyer-Crowley method and about landmark time points will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Binary proportions and associated confidence intervals will be estimated for within cohort objectives. With participants in Cohort 1 and 3 and participants in Cohort 2, binary proportions can be estimated to within 16% and 20% with 95% confidence, respectively.
Time frame: Up to 3 years
Overall survival
Will be estimated using the method of Kaplan-Meier. Confidence intervals about medians will be estimated using the Brookmeyer-Crowley method and about landmark time points will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Binary proportions and associated confidence intervals will be estimated for within cohort objectives. With participants in Cohort 1 and 3 and participants in Cohort 2, binary proportions can be estimated to within 16% and 20% with 95% confidence, respectively.
Time frame: Up to 3 years
Duration of response
Will be estimated using the method of Kaplan-Meier. Confidence intervals about medians will be estimated using the Brookmeyer-Crowley method and about landmark time points will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function. Binary proportions and associated confidence intervals will be estimated for within cohort objectives. With participants in Cohort 1 and 3 and participants in Cohort 2, binary proportions can be estimated to within 16% and 20% with 95% confidence, respectively.
Time frame: Up to 3 years
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