Multinational phase 1 trial of single-agent divarasib in advanced solid tumors with a KRAS G12C mutation

Divarasib (GDC-6036) is a covalent KRAS G12C inhibitor. The multinational phase 1 GO42144 trial evaluated divarasib in patients with locally advanced or metastatic solid tumors that harbor a KRAS G12C mutation. TRAEs occurred in 93% of patients, grade 3 TRAEs in 11%, grade 4 TRAE in one patient (1%), while there was no grade 5 TRAE. Among NSCLC patients, a confirmed response was observed in 53.4, and the median PFS was 13.1 months. Among CRC patients, a confirmed response was observed in 29.1%, and the median PFS was 5.6 months. Responses were also observed in patients with other solid tumors. The authors conclude that treatment with divarasib resulted in durable clinical responses across advanced KRAS G12C-positive tumors, with mostly low-grade adverse events.