SUNRAY-01, a pivotal, global study of olomorasib (LY3537982) in combination with pembrolizumab with or without chemotherapy for 1L treatment in KRAS G12 C-mutant advanced NSCLC (Trial in Progress)

Mutations in KRAS are among the most frequent oncogenic drivers with the G12C variant found in ~13% of NSCLC. Outcomes for KRAS G12C-mutant NSCLC may be improved by combining KRAS G12C inhibitors with current 1L standard of care (SOC). In the LOXO-RAS-20001 phase 1/2 study, olomorasib in combination with pembrolizumab demonstrated preliminary efficacy and a favorable safety profile.

SUNRAY-01 (NCT06119581) is a pivotal, global, phase 3 study in 1L advanced KRAS G12C-mutated NSCLC designed to seamlessly 1) optimize the dosing of olomorasib in combination with 1L SOC, and 2) compare efficacy and safety of olomorasib+SOC with placebo+SOC. In the open-label randomized dose optimization (pembrolizumab+olomorasib 50mg vs 100mg BID) and single arm safety lead-in (olomorasib+pembrolizumab, pemetrexed, platinum), the optimal dose of olomorasib for combination therapy will be determined before opening phase 3 study parts A and B. In part A, 384 participants with PD-L1 expression≥50% are randomized (1:1) to pembrolizumab+olomorasib or placebo. In part B, 552 participants are randomized (1:1) to pembrolizumab, pemetrexed, platinum+olomorasib or placebo regardless of PD-L1 expression. Allocation of participants with PD-L1 expression≥50% to either part A or part B will be at the discretion of the investigator. The primary objective is to compare efficacy based on PFS per RECIST v1.1 by blinded independent central review. Secondary endpoints include OS, ORR, DOR, DCR, TTR, PFS2, safety and tolerability, and patient-reported outcomes. Eligible participants (≥ 18 years): have KRAS G12C mutation in tumor or blood and known PD-L1 expression (0-100%); stage IIIB, IIIC, or IV NSCLC not suitable for curative intent radical surgery or radiation therapy; measurable disease per RECIST v1.1; ECOG PS 0-1; no prior systemic therapy for NSCLC, although 1 prior cycle of SOC treatment was allowed. The study opened for enrollment in December 2023.

Previously presented at ASCO 2024

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Artikel online veröffentlicht:
18. März 2025