CodeBreaK 101 Trial Evaluates Sotorasib Plus Chemotherapy in KRAS-Mutated NSCLC

Sotorasib (Lumakras) plus chemotherapy showed durable responses and was safe for patients with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC), according to updated findings from the CodeBreaK 101 clinical trial.

The phase 1b trial included 58 patients with a median age of 65.5 years who had an Eastern Cooperative Oncology Group performance status of 0 (38%) or 1 (62%). Nearly half (45%) of the patients enrolled were men. Prior to the trial, 86% of patients in the second-line setting had received anti-PD-(L)1 therapy.

Safety and tolerability were the primary endpoints. The secondary endpoints included 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).

Patients enrolled in the study received sotorasib 960 mg daily plus carboplatin AUC 5 intravenously every 3 weeks and pemetrexed 500 mg/m2 intravenously every 3 weeks for up to 4 cycles, followed by sotorasib plus pemetrexed maintenance until disease progression or unacceptable toxicity.

The updated analysis, which was presented during the 2024 American Society of Clinical Oncology Annual Meeting held May 31-June 4, 2024, in Chicago, Illinois, showed that 93% (n=54) of patients experienced a treatment-related adverse event (TRAE). Grade 3-4 TRAEs occurred in 52% (n=30) of the trial participants, with 1 death related to a TRAE.

The most common TRAEs were neutropenia (29%), thrombocytopenia (16%), and anemia (14%). Only 9% (n=5) of patients had to discontinue sotorasib treatment because of a TRAE.

Furthermore, for patients treated in the first-line setting (n=37), the ORR was 65%, the DCR was 100%, and the median DOR was 9.1 months. The median PFS was 10.8 months.

In the second-line setting (n=21), ORR was 42% and DCR was 84%. The median PFS was 8.3 months, but OS data remained immature for both groups.

“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,” the researchers said.

Reference

Li BT, Clarke JM, Felip E, et al. Sotorasib plus carboplatin and pemetrexed in KRAS G12C advanced NSCLC: Updated analysis from the international CodeBreaK 101 trial. Abstract #8512. Presented at the 2024 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2024, Chicago, Illinois.