This is a randomised, parallel-group, multicentre, open-label Phase III trial to compare the efficacy and safety of obrixtamig in combination with standard therapy (atezolizumab, carboplatin and etoposide) versus standard therapy without obrixtamig as first-line treatment in patients with ES-SCLC.

Randomization 1:1 to either the obrixtamig + atezolizumab, carboplatin, and etoposide treatment arm or the atezolizumab, carboplatin, and etoposide control arm. Participants in both arms will be treated with 1 cycle of platinum + etoposide with or without anti-PD-1/anti-PD-L1 standard therapy prior to randomisation.

The trial will compare obrixtamig in combination with atezolizumab, carboplatin, and etoposide vs. atezolizumab, carboplatin, and etoposide in participants with ES-SCLC. The primary objective is to demonstrate superiority in overall survival (OS) in at least 1 of 2 populations: 1) the overall population and 2) the DLL3 high (≥50% TC) population. The stratified logrank test and hazard ratio will be used to determine superiority. The primary comparison will be made for randomised participants, including the effects of treatment discontinuation, interruption of trial medication due to any reason, use of restricted medication or start of subsequent anti-cancer therapy, i.e. treatment policy strategy.

• Patients with histologically confirmed ES-SCLC who have completed 1 cycle of first-line treatment (platinum + etoposide, with or without anti-PD-1/anti-PD-L1 therapy, administered at a minimum dose of cisplatin 75 mg/m2 or carboplatin AUC 5 and etoposide 80 mg/m2)
• Patients without any previous systematic anti-cancer treatment for ES-SCLC (except for the completed 1 cycle of first-line treatment). Patients who received previous systematic anti-cancer treatment during limited stage are eligible if the treatment has been completed more than 6 months before the diagnosis of ES-SCLC.
• Adequate archival formalin-fixed paraffin-embedded (FFPE) tumour tissue, as specified in the Laboratory Manual, must be available for central laboratory analysis of DLL3 expression status and other biomarkers. The central laboratory investigational VENTANA DLL3 (SP347) RxDx test result must be available prior to randomisation.

• Presence of leptomeningeal disease and/or carcinomatous meningitis
• Previous treatment targeting DLL3 (e.g. TcEs, cell therapies, antibody-drug conjugates, or radiopharmaceuticals)
• Radiotherapy of any anatomical sites within 14 days prior to randomisation