TIGOS Trial: A Randomized, Double-Blind, Phase III Trial of Atigotatug and Nivolumab Fixed-Dose Combination With Chemotherapy Versus Atezolizumab With Chemotherapy as First-Line Therapy in Patients With Extensive-Stage Small Cell Lung Cancer.

[INTRODUCTION] Extensive-stage small cell lung cancer (ES-SCLC) is an aggressive malignancy with limited treatment options and poor outcomes. Despite the addition of antiprogrammed death ligand 1 inhibitors to platinum-etoposide chemotherapy, median overall survival (OS) remains < 1 year.

[PATIENTS AND METHODS] TIGOS (CA245-0001; NCT06646276) is an ongoing randomized, double-blind, multicenter phase III study evaluating a fixed-dose combination (FDC) of atigotatug and nivolumab (BMS-986489) plus carboplatin-etoposide chemotherapy compared with atezolizumab plus carboplatin-etoposide chemotherapy as first-line treatment for patients with ES-SCLC. Atigotatug is a monoclonal antibody acting as a tumor-targeted innate immune inducer that binds fucosyl-monosialoganglioside-1, which is expressed on ≤ 90% of SCLC tumor cells and minimally in normal tissues. Nivolumab, an antiprogrammed death-1 antibody, restores T-cell activity and promotes adaptive antitumor immunity. Together, these agents act through distinct but complementary immune mechanisms to enhance tumor cell killing. Approximately 530 adults (age ≥ 18 years) with histologically or cytologically confirmed ES-SCLC, ≥ 1 measurable extracranial lesion per RECIST v1.1, and an Eastern Cooperative Oncology Group performance status of 0-1 will be randomized 1:1 to receive either atigotatug and nivolumab FDC or atezolizumab in combination with carboplatin plus etoposide until progression, toxicity, or withdrawal. The primary endpoint is OS. The key secondary endpoint (statistically analyzed) is time to definitive deterioration; other secondary endpoints include progression-free survival, objective response, duration of response, and safety.

[CONCLUSION] Recruitment is ongoing at 182 sites across 26 countries with an estimated primary completion date of April 2028, with study completion in September 2031.