Solange Peters, Maximilian J. Hochmair, Kathryn C. Arbour, Luis Paz-Ares Rodríguez, Martin Reck, Ticiana Leal, C. Lindsay, Lu Shun, William Nassib William, Alexander I. Spira, Joshua K. Sabari, Bjørn Henning Grønberg, Makoto Nishio, Timothy F. Burns, Nicolas Girard, Frederico Capuzzo, A. Merced, Nicolas Fasnacht, Carla Visseren-Grul, Marcelo V. Negrão
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.