Sotorasib versus pembrolizumab in combination with platinum doublet chemotherapy as first-line treatment for metastatic or locally advanced, PD-L1 negative, KRAS G12C-mutated NSCLC (CodeBreaK 202).

person Fabrice Barlesi Gustave Roussy and Paris Saclay University, Faculty of Medicine, Villejuif / Kremlin-Bicêtre, France info_outline Fabrice Barlesi, Enriqueta Felip, Sanjay Popat, Benjamin J. Solomon, Juergen Wolf, Bob T. Li, Yi-Long Wu, Keith Kerr, Hiroaki Akamatsu, David Ross Camidge, Ravi G. Gupta, Alison Meloni, Tian Dai, Hossein Borghaei

Authors person Fabrice Barlesi Gustave Roussy and Paris Saclay University, Faculty of Medicine, Villejuif / Kremlin-Bicêtre, France info_outline Fabrice Barlesi, Enriqueta Felip, Sanjay Popat, Benjamin J. Solomon, Juergen Wolf, Bob T. Li, Yi-Long Wu, Keith Kerr, Hiroaki Akamatsu, David Ross Camidge, Ravi G. Gupta, Alison Meloni, Tian Dai, Hossein Borghaei Organizations Gustave Roussy and Paris Saclay University, Faculty of Medicine, Villejuif / Kremlin-Bicêtre, France, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron University Hospital, Barcelona, Spain, The Royal Marsden Hospital and The Institute of Cancer Research, London, United Kingdom, Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia, University Hospital of Cologne, Cologne, Germany, Memorial Sloan Kettering Cancer Center, New York, NY, Guangdong Lung Cancer Institute, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China, Aberdeen Royal Infirmary, Aberdeen, United Kingdom, Wakayama Medical University Hospital, Wakayama-Shi, NA, Japan, University of Colorado Cancer Center, Aurora, CO, Amgen Inc., Thousand Oaks, CA, Fox Chase Cancer Center, Philadelphia, PA Abstract Disclosures Research Funding Amgen, Inc. Background: The 5-year progression free survival (PFS) rate of patients with metastatic, PD-L1 negative, non-small cell lung cancer (NSCLC) remains poor, ranging from approximately 2% to 10% with standard immunotherapy-based treatment regimens. Based on promising anti-tumor activity in the phase 1 CodeBreaK 101 study, with partial responses observed in 62% (8/13) of PD-L1 negative patients in the first-line setting, we hypothesize that sotorasib plus platinum doublet chemotherapy will demonstrate durable clinical response and improved outcomes in this population. CodeBreaK 202 (NCT05920356) is a global phase 3 randomized study evaluating the efficacy of sotorasib versus pembrolizumab in combination with platinum doublet chemotherapy as first-line treatment for metastatic or locally advanced, PD-L1 negative, KRAS G12C-mutated NSCLC. Methods: Patients will be randomized 1:1 to either sotorasib 960 mg once daily or pembrolizumab administered in combination with carboplatin and pemetrexed for 4 cycles, followed by maintenance treatment with sotorasib or pembrolizumab administered in combination with pemetrexed. Key eligibility criteria include treatment-naïve metastatic or locally advanced stage IIIB/C disease that is not amenable to definitive chemoradiation, PD-L1 <1% expression, presence of KRAS G12C mutation, non-squamous tumor histology, and absence of actionable genomic alterations such as EGFR mutations and ALK rearrangements. Patients with both treated and untreated brain metastases are eligible if clinically asymptomatic. The primary endpoint is PFS per RECIST v1.1 by blinded independent central review (BICR). Key secondary endpoints include overall survival and objective response rate. Exploratory endpoints include intra-cranial PFS per RANO-BM criteria. Approximately 750 patients are planned to be enrolled and recruitment began on November 18, 2023. Contact Amgen Medical Information for more information: medinfo@amgen.com. Clinical trial information: NCT05920356.

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