Phase III Trial of BI 764532 Plus Atezolizumab, Carboplatin, and Etoposide as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer

The primary objective is to demonstrate superiority in overall survival in at least one of two populations: the overall population and the DLL3 high (≥50% TC) population. This endpoint is clinically relevant because it directly assesses whether the investigational combination improves survival in extensive-stage small cell lung cancer. The secondary objectives are to demonstrate superiority in progression-free survival and in the change from baseline at Week 19 in the dyspnea symptom scale of EORTC QLQ-LC13 in at least one of the same two populations; to evaluate objective response by estimating the odds ratio for the proportion of participants with response in at least one of the two populations; to assess time to deterioration in dyspnea, cough, and chest pain using EORTC QLQ-C30 and QLQ-LC13; to assess the change from baseline at Week 19 in the EORTC QLQ-LC13 chest pain and cough symptom scales; and to evaluate safety by describing the proportion of participants with treatment-emergent cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, treatment-emergent adverse events leading to trial medication discontinuation, dose delay, or dose reduction.

The trial population comprised 379 patients with small cell lung cancer. Both female and male participants were included, and the age range covered adult and older adult patients. The population was selected from patients with histologically confirmed extensive-stage disease who had completed 1 cycle of first-line platinum-etoposide treatment, with or without anti-PD-1/anti-PD-L1 therapy. Participants were required to have an ECOG performance status of 0 or 1 and adequate archival tumour tissue for central laboratory assessment of DLL3 expression and other biomarkers. Patients with asymptomatic brain metastases could be included if they met specified stability requirements. Further inclusion criteria applied.

The study is a Phase III, multicenter, open-label, randomized, controlled trial in patients with extensive-stage small cell lung cancer. It compares intravenous obrixtamig in combination with atezolizumab, carboplatin, and etoposide versus atezolizumab, carboplatin, and etoposide alone as first-line treatment. The primary objective is to demonstrate superiority in overall survival in at least one of two populations: the overall population and the DLL3 high population. The planned trial period extends from March 2026 to March 2029. Study participation begins with a screening visit to confirm eligibility, including histologic confirmation, review of prior treatment, assessment of performance status, availability of archival tumour tissue, and central laboratory determination of DLL3 expression. Eligible participants then enter randomization after completion of one cycle of first-line therapy. Follow-up visits are performed during treatment and after treatment to assess efficacy, safety, and patient-reported outcomes, including disease progression, adverse events, and symptom changes. An end-of-study visit is conducted at the end of participation to complete final assessments. Expected participant involvement is up to the duration required by the protocol and the overall study follow-up period. Early termination may occur in the event of disease progression, death, withdrawal of consent, loss to follow-up, discontinuation of trial medication because of adverse events, or other protocol-defined reasons.

Carboplatin is administered as a solution for infusion by intravenous infusion at a dose of 750 mg. Etoposide is administered as a solution for infusion by intravenous infusion at a dose of 100 mg/m2. Atezolizumab is administered as a solution for infusion by intravenous infusion at a dose of 1200 mg. BI 764532 is administered as a solution for infusion by intravenous infusion; the dose is listed as 00 mg. Tocilizumab is administered as a solution for infusion by intravenous infusion at a dose of 2400 mg and is used as an auxiliary treatment.

Efficacy will be assessed primarily by overall survival in at least one of two populations: the overall population and the DLL3 high (≥50% TC) population. Secondary efficacy assessments will include progression-free survival, defined as the time from randomisation until the earliest date of tumour progression according to RECIST version 1.1 based on investigator assessments or death from any cause, and overall response, defined as a best overall response of complete response or partial response according to RECIST 1.1 based on investigator assessments from the date of randomisation until the earliest date of disease progression, death, last evaluable tumour assessment before start of subsequent anti-cancer therapy, lost to follow-up, or withdrawal of consent.

Additional efficacy measures will include change from baseline to Week 19 in the dyspnea symptom subscale of the EORTC QLQ-LC13, and time to deterioration for symptom scales assessed by the EORTC QLQ-C30 and EORTC QLQ-LC13, including dyspnea, chest pain, and cough. Change from baseline to Week 19 in the chest pain and cough symptom scales of the EORTC QLQ-LC13 will also be evaluated.