SUNRAY-02: a study of olomorasib combined with immunotherapy in stage II-III KRAS G12C-mutant non-small cell lung cancer after definitive therapy.

More than half of patients with early-stage non-small cell lung cancer (NSCLC) experience recurrent disease following definitive therapy. Targeted therapies have demonstrated significant and clinically meaningful benefit in EGFR-, ALK-, or RET-driven early-stage NSCLC. There are, however, no approved therapies for early-stage KRAS G12C-mutant NSCLC, presenting a potential therapeutic opportunity. Olomorasib is a potent, highly selective next-generation KRAS G12C inhibitor(i) demonstrating promising antitumor and intracranial activity with a manageable safety profile in KRAS G12C-mutant metastatic NSCLC. Preclinical studies have shown that KRAS G12C inhibition reverses KRAS-mediated immune suppression, creating an inflamed tumor microenvironment responsive to immunotherapy. Combining olomorasib and immune checkpoint inhibitors is supported by synergistic and additive effects in preclinical and clinical setting. SUNRAY-02 is a 2-part global, placebo-controlled phase III study recruiting patients with stage II-III KRAS G12C-mutant NSCLC following definitive therapy. Part A patients with resected NSCLC receive olomorasib or placebo in combination with pembrolizumab, while Part B patients with unresectable NSCLC receive olomorasib or placebo in combination with durvalumab. Combination treatment continues for approximately 1-year, followed by olomorasib or placebo monotherapy, completing up to 3-years of treatment. This trial addresses a critical treatment gap in KRAS G12C-mutant early-stage NSCLC.Clinical trial registration: NCT06890598 (www.clinicaltrials.gov); EudraCT: 2024-512302-25-00.