Phase III Trial of BI 764532 Plus Carboplatin and Etoposide Versus Carboplatin and Etoposide in Previously Untreated DLL3-Positive Advanced Extrapulmonary Neuroendocrine Carcinoma

The primary objective is to demonstrate the superiority of overall survival for obrixtamig in combination with carboplatin and etoposide versus carboplatin and etoposide alone in previously untreated patients with unresectable locally advanced or metastatic extrapulmonary neuroendocrine carcinoma that is DLL3-positive. This endpoint is clinically relevant because it evaluates whether the investigational regimen prolongs survival compared with standard chemotherapy. The secondary objectives are to demonstrate superiority in progression-free survival and to assess patient-reported physical functioning at Week 19 using the EORTC QLQ-C30.

The trial population comprised 246 patients with unresectable locally advanced or metastatic extrapulmonary neuroendocrine carcinoma. Both female and male participants were included, and the age range was 18 years and older. The population was selected from patients with poorly differentiated disease, ECOG performance status 0 or 1, no prior systemic treatment for unresectable locally advanced or metastatic disease except one completed cycle of standard platinum plus etoposide, and adequate archival tumour tissue with confirmed DLL3 expression. Patients with mixed histologies were eligible only when the neuroendocrine carcinoma component was predominant. No information was provided on general health status beyond these eligibility requirements or on lifestyle factors such as diet, physical activity, or habits.

This is a Phase III, multi-center, open-label, randomized, controlled trial in previously untreated, DLL3-positive patients with unresectable locally advanced or metastatic extrapulmonary neuroendocrine carcinoma. Participants are assigned to receive intravenous obrixtamig in combination with carboplatin and etoposide or carboplatin and etoposide alone. The primary objective is to compare overall survival. The overall trial duration is estimated from 26 June 2026 to 15 May 2030. Study participation begins with a screening visit to confirm eligibility, including disease characteristics, prior treatment status, performance status, and central laboratory assessment of DLL3 expression. After randomization, treatment and protocol assessments are performed during follow-up visits, with evaluation of survival, disease progression, response, and safety, including treatment-emergent adverse events, cytokine release syndrome, and immune effector cell-associated neurotoxicity syndrome. An end-of-study visit is conducted at the end of protocol participation to complete final assessments. Expected participant involvement extends from screening through treatment and follow-up until the end-of-study visit, or until earlier discontinuation. Early termination may occur because of disease progression, death, withdrawal of consent, loss to follow-up, start of next-line anti-cancer treatment, or treatment discontinuation due to adverse events or other protocol-defined reasons.

The investigational treatment consisted of obrixtamig (BI 764532), a solution for infusion administered by intravenous infusion. The source data did not specify the dose, frequency, or dosing schedule for this agent. The trial also included carboplatin as a solution for infusion administered by intravenous infusion at a dose of 750 mg, and etoposide as a solution for infusion administered by intravenous infusion at a dose of 100 mg/m². The administration frequency for these agents was not specified in the source data.

The non-experimental treatment was tocilizumab (Avtozma 20 mg/mL concentrate for solution for infusion), provided as a solution for infusion for intravenous infusion at a dose of 2400 mg. The source data did not specify the dosing schedule or any additional administration details. Information on participant compliance monitoring was not provided in the source data.

Efficacy will be assessed by overall survival, defined as the time from randomisation until death from any cause. Additional efficacy assessments will include progression-free survival, defined as the time from randomisation until the earliest date of disease progression according to RECIST 1.1 based on investigator assessments or death from any cause, whichever occurs first. Objective response will be evaluated as the best overall response of complete response or partial response according to RECIST 1.1 based on investigator assessments, and disease control will be assessed as the best overall response of complete response, partial response, or stable disease according to RECIST 1.1 based on investigator assessments. Duration of response will be measured from the first documented objective response until disease progression or death. Change from baseline to Week 19 in the physical functioning domain of the EORTC QLQ-C30 will also be assessed.