Seguridad y eficacia de sotorasib en combinación con panitumumab y FOLFIRI en pacientes con cáncer colorrectal metastásico con mutación KRAS G12C previamente tratados, en el estudio CodeBreaK 101 de fase Ib.

In the phase III CodeBreaK 300 trial (NCT05198934), the combination of sotorasib, a KRASG12C inhibitor, and panitumumab improved clinical outcomes in patients with chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC). CodeBreaK 101 (NCT04185883) is a phase Ib trial wherein irinotecan, leucovorin, and 5-fluorouracil (FOLFIRI) was added to sotorasib and panitumumab in previously treated patients with KRAS G12C-mutated mCRC. Patients with KRAS G12C-mutated mCRC who received ≥1 prior systemic treatment were enrolled in CodeBreaK 101 subprotocol H dose-exploration and dose-expansion cohorts. In the dose-exploration cohort, patients received sotorasib (960 mg orally daily) plus panitumumab [6 mg/kg i.v.

Q2W] and standard dose FOLFIRI (i.v. Q2W). This initial dose level was declared the recommended phase II dose and used in the dose-expansion cohort. The primary endpoint was safety, and secondary endpoints were efficacy and pharmacokinetics.

A total of 46 patients were enrolled into the dose-exploration (n = 6) and dose-expansion (n = 40) cohorts [n = 21 (46%) female, median age, 54.0 (range, 36-76)]. Patients had received a median of two prior lines of therapy (range, 1-6) with approximately one-third each receiving the study regimen as second-, third-, or fourth-line-or-greater therapy. No dose-limiting toxicities were observed in the dose-exploration cohort at the initial dose level. In the 46 patients in both dose-exploration and dose-expansion cohorts, grade ≥3 treatment-related adverse events (TRAEs) occurred in 23 (50%) patients.

The most common TRAEs were dermatitis acneiform (65.2%), dry skin (60.9%), and neutrophil count decreased/neutropenia (56.5%). Confirmed overall response rate was 56.5% [95% confidence interval (CI) 41.1-71.1], median progression-free survival was 8.3 months (95% CI 7.0-11.0), and median overall survival was 17.9 months (95% CI 13.0-23.3). Sotorasib plus panitumumab and FOLFIRI demonstrated a manageable safety profile and promising antitumor activity in previously treated patients with KRAS G12C-mutated mCRC.