Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2026

First-line (1L) olomorasib + pembrolizumab in KRAS G12C-mutant NSCLC: updated results from LOXO-RAS-20001 and SUNRAY-01     (146292)

Melissa L. Johnson 1 , Luis Mateos 2 , Tadaaki Yamada 3 , Neeharika Makani 4 , Bryan Chan 5 , Wen-Tsung Huang 6 , Dionisios Spyratos 7 , Jaromir Roubec 8 , Niels Reinmuth 9 , Adrian Sacher 10 , Alexander I. Spira 11 , Nimit Singhal 12 , Shinji Takeuchi 13 , Yonina Murciano-Goroff 14 , Yanhong Zhou 15 , Aaron A. Fink 15 , Alyson Merced 15 , Melinda D. Willard 15 , Carla Visseren-Grul 15 , Solange Peters 16 , Aarohan Pruthi 17
  1. Sarah Cannon and HCA Research Institute, Nashville, TN, USA
  2. Hospital Clínico Universitario de Santiago, Health Research Institute of Santiago de Compostela (IDIS), Municipality of Santiago de Compostela , Spain
  3. Department of Pulmonary Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
  4. Comprehensive Hematology-Oncology, St. Petersburg, FL, USA
  5. The Adem Crosby Cancer Centre, Sunshine Coast University Hospital, Sunshine Coast, Queensland, Australia
  6. Chi Mei Chest Hospital, Tainan, Taiwan
  7. Pulmonary Department, Lung Cancer Oncology Unit, Aristotle University of Thessaloniki, G. Papanicolaou Hospital, Thessaloniki, Greece
  8. Nemocnice AGEL Ostrava-Vítkovice, Ostrava, Czech Republic
  9. Asklepios Lung Clinic, Munich-Gauting, Germany
  10. Department of Medical Oncology, Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, ON, Canada
  11. Virginia Cancer Specialists, Fairfax, VA, USA
  12. Icon Cancer Centre Adelaide, South Brisbane, Queensland, Australia
  13. Kanazawa University Hospital, Kanazawa, Japan
  14. Department of Medicine, Memorial Sloan Kettering Cancer Center , New York, NY, USA
  15. Eli Lilly and Company, Indianapolis, IN, USA
  16. Oncology Department, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
  17. Eli Lilly, Sydney, NSW, Australia

Aims: We report updated results, with 9-months additional follow-up, in 1L patients who received olomorasib (a KRAS G12C inhibitor) + pembrolizumab from the dose optimization cohorts of LOXO-RAS-20001 and SUNRAY-01.

Methods: Patients with advanced KRAS G12C-mutant NSCLC (ECOG PS 0-1) and PD-L1 expression 0-100% were randomized to receive olomorasib 50 or 100 mg, orally BID with pembrolizumab 200 mg Q3W. Patients who received 1 cycle of pembrolizumab prior to enrollment were eligible. Primary endpoint: safety. Secondary endpoints: ORR per RECIST v1.1, DOR, and PFS. 

Results: As of 5-March-2026, 85 patients received olomorasib + pembrolizumab (16% received 1 prior cycle of pembrolizumab; 64% were PD-L1 ≥50). The median follow-up time was 20.7 months (IQR,18.0-23.0). ORR was 73% in all patients (n=84; PD-L1 0-100%), 78% in patients with PD-L1 ≥50% (n=54). Responses were durable across all patients; median DOR and PFS were not reached, with a 6-, 12-, and 18-month PFS rate of 77%, 65% and 55%, respectively. No new safety signals were identified. Any-grade TRAEs (in ≥20% of patients): diarrhea (33%), ALT/AST increased (27%/25%). Most common grade ≥3 TRAEs: ALT/AST increased (16%/14%), diarrhea (8%). Hepatic events were manageable with dose adjustments and/or corticosteroids. TRAEs led to olomorasib dose reduction in 34% patients and discontinuation of combination treatment in 12%.  

Conclusions: Olomorasib + pembrolizumab continues to demonstrate durable efficacy and a manageable safety profile. These updated findings provide additional support for the ongoing Phase 3 SUNRAY-01 trial, comparing pembrolizumab + olomorasib or placebo as 1L treatment in patients with KRAS G12C-mutant NSCLC and PD-L1 ≥50%.