Poster Presentation Clinical Oncology Society of Australia Annual Scientific Meeting 2026

Intracranial efficacy of olomorasib, a next-generation KRAS G12C inhibitor, in patients with KRAS G12C-mutant NSCLC who have active, untreated brain metastases   (146295)

Phillipe Cassier 1 , Jeffrey Schneider 2 , Antoine Italiano 3 , Antoine Hollebecque 4 , Rebecca Heist 5 , Toshio Shimizu 6 , So Yeon Kim 7 , Alexander Spira 8 , Rasha Cosman 9 , Garrett Sherwood 10 , Shetal Patel 11 , Young-Chul Kim 12 , Wade Iams 13 , Maya Khalil 14 , Aaron Fink 15 , Yan Lin 15 , Melinda D. Willard 15 , Mark Socinski 16 , Aarohan Pruthi 17
  1. Centre Leon Berard, France
  2. NYU Langone Hospital – Long Island, USA
  3. Institut Begonie, France
  4. Gustave Roussy, France
  5. Massachusetts General Hospital, USA
  6. Wakayama Medical University Hospital, Japan / Kansai Medical University Hospital, Japan
  7. Yale University School of Medicine, Yale Cancer Center, USA
  8. Virginia Cancer Specialists, USA
  9. The Kingdom Cancer Centre , Australia
  10. Novant Health, USA
  11. University of North Carolina, Chapel Hill, USA
  12. Chonnam National University Hwasun Hospital, South Korea
  13. Tennessee Oncology, USA
  14. University of Alabama, USA
  15. Eli Lilly and Company, Indianapolis, IN, USA
  16. Advent Health, USA
  17. Eli Lilly, Sydney, NSW, Australia

Aims: We present updated results on the intracranial efficacy of olomorasib, a KRAS G12C inhibitor, in patients with KRAS G12C-mutant NSCLC with active, untreated brain metastases from the phase 1/2 LOXO-RAS-20001 (NCT04956640) study.

Methods: ECOG 0-1 and KRAS G12C inhibitor-naïve patients with advanced NSCLC positive for KRAS G12C (tissue or plasma) with active, untreated brain metastases received single agent olomorasib (150 mg BID). Safety was assessed in all treated patients. Intracranial response by modified RECIST v1.1 in ≥1 measurable (≥5 mm) intracranial lesion was evaluated in patients with at least one post-baseline response assessment or who discontinued treatment before the first assessment.

Results: As of 15January2025, 19 patients (median age 65 yrs, range 42-80) were treated. 15 patients had prior systemic therapy - 13 in the metastatic setting; 8 patients had ≥2 lines of therapy. Median number of intracranial target lesions was 1 (range, 1-3). Safety was consistent with previous reports of olomorasib. The most common TRAEs (>15%) were low-grade diarrhea, fatigue and nausea; no grade ≥3 TRAEs were observed. Among the 18 efficacy-evaluable patients, intracranial objective response rate was 44.4% (8/18 patients; 95%CI:21.5-69.2; 1 CR, 5 PR, 2 uPR pending/ongoing) and disease control rate was 83.3% (15/18 patients; 95%CI,58.6-96.4; 7 SD). Median time to intracranial response was 2.0 months (range 1.3-3.9) and median duration of response and progression-free survival were not yet reached (5.4 months median follow-up for intracranial response; 95%CI:2.79-NE).

Conclusions: Olomorasib continues to demonstrate promising intracranial activity and disease control in patients with KRAS G12C-mutant NSCLC and active, untreated brain metastases. These results support continued clinical development of olomorasib in patients with KRAS G12C-mutant NSCLC including in patients with brain metastases. Two global registrational studies investigating olomorasib in combination with immunotherapy in first-line metastatic and early-stage NSCLC are ongoing (NCT06119581 and NCT06890598).