Aims:
We report updated results, with an additional 9-months of follow-up, in 1L patients who received olomorasib (a KRAS G12C inhibitor) + chemo-IO from LOXO-RAS-20001 and the SUNRAY-01 safety lead-in.
Methods:
Patients with advanced KRAS G12C-mutant NSCLC, PD-L1 0-100%, and ECOG PS 0-1 received olomorasib 50/100mg orally BID with pembrolizumab + chemotherapy (per label). Patients who received one cycle of SOC prior to enrollment were eligible. Primary endpoint: safety. Secondary endpoints: ORR per RECIST v1.1, DOR, and PFS.
Results:
As of 5March2026, 77 patients received olomorasib + chemo-IO; 25 patients (32%) received 1 prior cycle of SOC; PD-L1 expression: 34% were <1%, 40% were 1-49%, and 23% were ≥50% (3% unknown). Median follow-up was 18.7 months (IQR:16.8-20.3). ORR was 61% (47/77), with a mDOR of 14.5 months and mPFS of 11.8 months. Efficacy by PD-L1 expression: ORR was 50% (13/26) in patients with PD-L1 <1% (mDOR:14.4 months; mPFS:9.7 months), 68% (21/31) in patients with PD-L1 1–49% (mPFS:12.1 months), and 67% (12/18) in patients with PD-L1 ≥50%. Any grade TRAEs (≥20% of patients): nausea (44%), anemia (39%), fatigue (39%), diarrhea (32%), AST/ALT increased (31%/27%). Most common grade ≥3 TRAEs: anemia (16%), neutrophil count decreased (12%), ALT/AST increased (12%/10%). TRAEs led to olomorasib dose reduction in 21% patients; and discontinuation of all study treatment in 8% patients.
Conclusions:
Olomorasib + chemo-IO continues to demonstrate durable efficacy and a manageable safety profile across PD-L1 levels, including in higher-risk patients with PD-L1 0-49%. These updated findings support the ongoing Phase 3 SUNRAY-01 trial comparing 1L chemo-IO + olomorasib or placebo in patients with KRAS G12C-mutant NSCLC and PD-L1 0-100%.