CodeBreaK 101 trial evaluating sotorasib in combination with chemotherapy in KRAS-mutated non-small cell lung cancer

The CodeBreaK 101 trial evaluated sotorasib (AMG510) in combination with chemotherapy in patients with KRAS-mutated non-small cell lung cancer (NSCLC). According to the latest research findings, this treatment regimen shows durable responses and a good safety profile for patients with advanced KRAS G12C-mutated NSCLC.

In the Phase 1b trial, there were 58 participants with an average age of 65.5 years, with 38% of patients exhibiting Eastern Cooperative Oncology Group status 0 and 62% having status 1. Nearly half (45%) of the patients were male. Before the start of the trial, 86% of second-line patients had received anti-PD-1 therapy. The primary endpoint of this trial is to evaluate the safety and tolerability of the treatment. Secondary endpoints include objective response rate (ORR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS) and overall survival (OS) for each investigator according to RECIST v1.1.

Patients participating in the trial received daily 960 mg of sotoracib, intravenous injection of carboplatin AUC 5 (Carboplatin) every 3 weeks, and intravenous injection of pemetrexed (Pemetrexed) 500 mg/m2 every 3 weeks for up to 4 cycles of treatment, and then switched to maintenance therapy of sotorasibu plus pemetrexed until disease progression or unacceptable toxicity.

Updated analysis as of2024 Society of Clinical Oncology Annual Meeting shows that 93% of patients (n=54) experienced treatment-related adverse events (TRAE), of which 52% of participants experienced grade 3-4 adverse events, and even one death was related to a treatment-related adverse event. Common adverse events included neutropenia (29%), thrombocytopenia (16%), and anemia (14%). Only 9% of patients (n = 5) had to discontinue treatment with sotoraxib due to adverse events.

In addition, among patients receiving first-line treatment (n=37), the objective response rate reached 65%, the disease control rate was 100%, the median duration of response was 9.1 months, and the median disease-free survival was 10.8 months. In second-line treatment, the objective response rate was 42%, the disease control rate was 84%, and the median progression-free survival was 8.3 months. However, overall survival data for patients in both groups are immature.

Sotorasibu plus platinum dual chemotherapyThe CodeBreaK 101 trial demonstrated strong and durable treatment responses with a manageable safety profile, which supports the ongoing CodeBreaK Phase 202 trial. The trial is designed to evaluate the efficacy of this treatment regimen in treatment-naïve, PD-L1-negative, KRAS G12C-mutated, advanced non-small cell lung cancer patients.