Eli Lilly presents updated data from Phase 1/2 study of Olomorasib

Eli Lilly announced updated data from the Phase 1/2 clinical trial evaluating olomorasib as a monotherapy in patients with KRAS G12C-mutant advanced solid tumors and in combination with Merck’s anti-PD-1 therapy KEYTRUDA in patients with KRAS G12C-mutant advanced non-small cell lung cancer. Olomorasib is an investigational, oral, potent, and highly selective second-generation inhibitor of the KRAS G12C protein. These data will be shared in oral presentations at the 2024 American Society of Clinical Oncology Annual Meeting. Results presented at ASCO utilized a cutoff date of March 18, 2024. Efficacy results are based on investigator response assessments, and objective response rates include responses that are confirmed, as well as those pending confirmation and ongoing. An oral presentation detailed updated data for olomorasib monotherapy in patients with KRAS G12C-mutant advanced solid tumors. This dataset consisted of 184 patients, including 42 with NSCLC naive to a KRAS G12C inhibitor, 41 with NSCLC who had received a prior KRAS G12C inhibitor, 32 with colorectal cancer, 24 with pancreatic cancer, and 45 with other solid tumors. Patients had received a median of three prior lines of therapy. Efficacy for olomorasib monotherapy was consistent across a range of solid tumors with an ORR of 35% in patients with non-CRC solid tumors. Median progression free survival in all patients with KRAS G12C inhibitor-naive non-CRC solid tumors was 7.1 months and 7.9 months in patients with KRAS G12C inhibitor-naive NSCLC. In patients with NSCLC previously treated with a KRAS G12C inhibitor, the ORR was 41%, with 63% having received a KRAS G12C inhibitor as their immediate prior therapy, and median PFS was 8.1 months. Preliminary CNS activity was seen, with CNS responses observed in patients with NSCLC and measurable brain metastases. Patients were on treatment for a median of 4.7 months and treatment-related adverse events were predominantly grade 1 with only diarrhea seen in greater than 15% of patients. The safety profile for patients who discontinued a prior KRAS G12C inhibitor due to toxicity was similar to all patients treated with olomorasib monotherapy including patients who discontinued their previous first KRAS G12C inhibitor due to toxicity. TRAEs led to discontinuation of olomorasib in 1% of patients. An oral presentation detailed updated data for olomorasib in combination with pembrolizumab in patients with KRAS G12C-mutant advanced NSCLC, studying the two doses under ongoing investigation in first-line NSCLC. This dataset consisted of 64 patients, including patients with first-line metastatic disease and those previously treated. Patients received a median of two prior lines of therapy. In patients with first-line metastatic NSCLC, across a range of PD-L1 levels, the ORR for olomorasib in combination with pembrolizumab was 77% and median PFS was not reached with follow-up ongoing. TRAEs led to discontinuation of olomorasib only in 3% of patients, pembrolizumab only in 11% of patients and both drugs in 5% of patients. The SUNRAY-01 trial, a global, registrational study investigating olomorasib in combination with pembrolizumab or pembrolizumab plus chemotherapy in first-line NSCLC, is currently enrolling.