Phase III CodeBreaK 200 trial of Lumakras shows improved PFS and ORR in KRAS G12C-mutated non small cell lung cancer

Lumakras significantly improved PFS as determined by Blinded Independent Central Review (BICR) compared to docetaxel in heavily pre-treated patients (median PFS of 5.6 vs 4.5 months respectively; HR, 0.66 [95% CI: 0.51, 0.86]; P = 0.002). PFS favored Lumakras across all clinically relevant subgroups, including those with a history of brain metastases at baseline. The proportion of patients with PFS at one year was 25% for Lumakras versus 10% for docetaxel.

Lumakras demonstrated a significantly higher ORR than docetaxel with double the response rates in the Lumakras arm (28% versus 13%, respectively; P < 0.001) and showed consistent benefit across other efficacy secondary endpoints, specifically improved disease control rate (DCR; 83% versus 60%, respectively); faster time to response (TTR; 1.4 versus 2.8 months, respectively); and longer duration of response (DOR; 8.6 versus 6.8 months, respectively). Overall survival (OS; a key secondary endpoint) was not significantly different between treatment arms (10.6 versus 11.3 months, respectively; HR, 1.01 [95% CI: 0.77, 1.33]; P = 0.53). The study was not powered to detect a statistical difference in OS, and more than one-third of patients on docetaxel went on to receive a KRASG12C inhibitor, either in protocol cross-over (26.4%) or as subsequent therapy (7.5%). A clinically meaningful improvement in patient reported outcomes was also observed with Lumakras versus docetaxel. Change over time (improvement from baseline to week 12) in global health status, physical functioning and dyspnea favored Lumakras. Time to deterioration (delaying symptoms from getting worse) in global health status, physical functioning and cancer-related symptoms (dyspnea and cough) were delayed with Lumakras compared to docetaxel. There were fewer treatment-related adverse events (TRAEs) for Lumakras versus docetaxel. These data were presented at the Presidential Symposium III session as a late-breaker oral presentation (#LBA5812) during the European Society for Medical Oncology (ESMO) Congress 2022 in Paris.