Divarasib Delivers 56% ORR and ~14 mo PFS in KRAS G12C NSCLC

Divarasib (GDC-6036) is an oral, covalent KRAS G12C inhibitor; targeting the ~11‑13% of NSCLC tumors that carry this mutation; in the GO42144 Phase I dose-escalation/expansion trial (NCT04449874) 65 previously treated advanced NSCLC patients received 50–400 mg once daily. After ≥12 months follow-up, 63 evaluable patients showed a confirmed ORR of 55.6% and median DoR of 18.0 mo; median PFS was 13.8 mo overall (15.3 mo at the 400 mg RP2D). Safety remained manageable with no new grade ≥3 toxicities. For context, the approved first-generation inhibitors sotorasib (ORR 41%, mPFS 6.3 mo)and adagrasib (ORR 43%, mPFS 6.9 mo) show roughly half the depth and durability of response in similar settings.