SUNRAY-01 trial protocol: an innovative study design of olomorasib and pembrolizumab with or without chemotherapy in KRAS G12C NSCLC

Olomorasib (LY3537982) is a potent, highly selective, next-generation oral inhibitor of KRAS G12C that has demonstrated promising antitumor and intracranial activity as well as a manageable safety profile in combination with immunotherapy or chemoimmunotherapy for first-line treatment of KRAS G12C-mutant advanced non-small cell lung cancer (NSCLC). Here we describe the design and rationale of SUNRAY-01, a pivotal, global trial of olomorasib in combination with pembrolizumab with or without chemotherapy for first-line treatment of KRAS G12C-mutant advanced NSCLC. Given that outcomes with KRAS G12C inhibitors remain dismal, this trial will assess whether combining olomorasib with existing standard-of-care treatment can improve outcomes in first-line KRAS G12C-mutant NSCLC. SUNRAY-01 has an innovative design, incorporating two phase III trials in a single protocol to address the full spectrum of current first-line treatment options, and includes pragmatic elements to reduce potential barriers to enrollment, such as permitting enrollment based on local testing by liquid or tissue biopsy, allowing treatment with 1 cycle of standard-of-care during screening prior to enrollment, allowing patients with small untreated or previously treated brain metastases, and ensuring both arms receive standard treatment.Clinical trial registration www.clinicaltrials.gov identifier is NCT06119581. EudraCT: 2023-503412-33–00.