Novel KRAS G12C inhibitor shows promising antitumour activity in mutated pancreatic cancer

The investigational KRAS G12C inhibitor sotorasib appears to be active against previously treated KRAS p.G12C–mutated advanced pancreatic cancer while having an acceptable safety profile, according to the results of a phase I/II trial.

The trial included 38 patients with pancreatic cancer positive for KRAS p.G12C mutation, all of whom had received at least one previous systemic therapy. The patients received sotorasib at a dose of 960 mg orally once daily in the trial’s second phase, for which the primary endpoint was a centrally confirmed objective response (complete or partial).

Efficacy endpoints were evaluated in the pooled population and included objective response, duration of response, time to objective response, disease control (defined as an objective response or stable disease), progression-free survival (PFS), and overall survival (OS). Safety was also assessed.

All 38 patients had metastatic disease at baseline and had previously received chemotherapy (median of 2 lines). Treatment with sotorasib produced a centrally confirmed objective response in eight patients (21 percent, 95 percent confidence interval [CI], 10–37). The median PFS was 4.0 months (95 percent CI, 2.8–5.6), while the median OS was 6.9 months (95 percent CI, 5.0–9.1).

Sixteen patients had treatment-related adverse events of any grade (42 percent), including six with grade 3 adverse events (16 percent). None of the treatment-related adverse events led to death or treatment discontinuation.