Sotorasib plus carboplatin and pemetrexed in KRAS G12C advanced NSCLC: Updated analysis from the international CodeBreaK 101 trial.

person Bob T. Li Memorial Sloan Kettering Cancer Center, New York, NY info_outline Bob T. Li, Jeffrey Melson Clarke, Enriqueta Felip, Jose Carlos Ruffinelli, Pilar Garrido, Jon Zugazagoitia, Sarah B. Goldberg, Suresh S. Ramalingam, Iván Victoria, Sonam Puri, David R. Gandara, William Kormany, Sophie Edmonds, Kerry Palmer, Ravi G. Gupta, Ramaswamy Govindan

Authors person Bob T. Li Memorial Sloan Kettering Cancer Center, New York, NY info_outline Bob T. Li, Jeffrey Melson Clarke, Enriqueta Felip, Jose Carlos Ruffinelli, Pilar Garrido, Jon Zugazagoitia, Sarah B. Goldberg, Suresh S. Ramalingam, Iván Victoria, Sonam Puri, David R. Gandara, William Kormany, Sophie Edmonds, Kerry Palmer, Ravi G. Gupta, Ramaswamy Govindan Organizations Memorial Sloan Kettering Cancer Center, New York, NY, Duke University, Durham, NC, Vall d’Hebron University Hospital, Barcelona, Spain, Institut Català d'Oncologia L´Hospitalet, Barcelona, Spain, Ramón y Cajal University Hospital, Madrid, Spain, Hospital Universitario 12 de Octubre, Madrid, Spain, Yale School of Medicine, New Haven, CT, Winship Cancer Institute of Emory University, Atlanta, GA, Hospital Clinic Barcelona, Barcelona, Spain, Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, University of California, Davis Comprehensive Cancer Center, Sacramento, CA, Amgen Inc., Thousand Oaks, CA, Amen Ltd., Cambridge, United Kingdom, Amgen Ltd., Cambridge, United Kingdom, Washington University School of Medicine in St. Louis, St. Louis, MO Abstract Disclosures Research Funding Amgen Inc Background: The combination of platinum doublet chemotherapy with sotorasib may improve anti-tumor activity and overcome therapeutic resistance in KRASG12C-mutated advanced non-small cell lung cancer (NSCLC). We report updated efficacy and safety of sotorasib plus carboplatin and pemetrexed from the international CodeBreaK 101 phase 1b trial (NCT04185883). Methods: Patients (Pts) with KRAS G12C-mutatedadvanced NSCLC received sotorasib 960 mg QD plus carboplatin AUC 5 IV Q3W and pemetrexed 500 mg/m2 IV Q3W for up to 4 cycles followed by sotorasib plus pemetrexed maintenance until disease progression/unacceptable toxicity. Data were analyzed by prior therapy in the locally advanced/metastatic setting (1L and 2L+). Primary endpoints were safety/tolerability. Secondary endpoints were objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) according to RECIST v1.1 per investigator, and overall survival (OS). Results: As of December 1, 2023, 58 pts (median age, 65.5 yrs; 45% male; ECOG status 0/1, 38%/62%) were treated with sotorasib plus carboplatin and pemetrexed; 37 (64%) pts in the 1L and 21 (36%) in the 2L+ setting. In 2L+, 18/21 (86%) pts had received prior anti-PD-(L)1 therapy. Treatment-related adverse events (TRAEs) occurred in 54 (93%) pts; grade 3–4 in 30 (52%) pts and fatal in 1 (2%) (Table). In 1L, ORR was 65% (95% CI, 46.5–80.3), DCR was 100%, median DOR was 9.1 mo (95% CI, 4.4–12.5), and median PFS was 10.8 mo (95% CI, 5.4–NE; median follow-up [f/u], 9.2 mo). Median PFS was 11.9 mo (95% CI, 5.3–NE) in the PD-L1 <1% subgroup (n=19). For 2L+, ORR was 42% (95% CI, 20.3–66.5), DCR was 84%, median DOR was NE, and median PFS was 8.3 mo (95% CI, 4.1–NE; median f/u, 4.4 mo). OS data remained immature. Conclusions: Sotorasib plus platinum doublet chemotherapy conferred robust and durable responses with a manageable safety profile in CodeBreaK 101, supporting evaluation of this regimen in the ongoing CodeBreaK 202 phase 3 trial in treatment naïve, PD-L1 negative, KRAS G12C-mutated advanced NSCLC (NCT05920356). Clinical trial information: NCT04185883. Key safety findings. n (%) 1L (n=37) 2L+ (n=21) Total (N=58) TRAEs, any grade 34 (92) 20 (95) 54 (93) Grade 3–4 18 (49) 12 (57) 30 (52) Fatal* 0 1 (5) 1 (2) Grade ≥3 TRAE in >10% overall Neutropenia/Neutrophil count decreased 11 (30) 6 (29) 17 (29) Thrombocytopenia/Platelet count decreased 6 (16) 3 (14) 9 (16) Anemia 6 (16) 2 (10) 8 (14) TRAE leading to discontinuation of sotorasib / carboplatin / pemetrexed / any study drug 2 (5) / 0 / 7 (19) / 8 (22) 3 (14) / 1 (5) / 5 (24) / 6 (29) 5 (9) / 1 (2) / 12 (21) / 14 (24) *Fatal TRAE was febrile neutropenia, attributed to carboplatin and pemetrexed.