Phase 3 obrixtamig DLL3×CD3 bispecific T‑cell engager plus platinum/etoposide in DLL3+ epNEC

Boehringer Ingelheim’s multicenter, open-label, randomized Phase 3 trial (NCT07544654) tests whether adding obrixtamig—an IgG-like DLL3×CD3 bispecific antibody that redirects T cells to kill DLL3-expressing tumor cells—improves outcomes versus chemotherapy alone in first-line, unresectable locally advanced or metastatic extrapulmonary neuroendocrine carcinomas (epNEC) that are DLL3-positive by immunohistochemistry. Patients are randomized 1:1 to obrixtamig + carboplatin (a platinum DNA crosslinking agent) + etoposide (a topoisomerase II inhibitor) followed by obrixtamig maintenance (up to ~3 years) versus carboplatin + etoposide alone (about 4 months). The study also evaluates a companion diagnostic-type device intended to measure DLL3 levels, which is commercially important because response to DLL3-directed T-cell engagers appears biomarker-linked and a validated assay could standardize patient selection across centers. The scientific angle is moving a DLL3-targeted T-cell engager earlier (frontline) in a setting where outcomes remain poor and treatment options are limited. Today’s care for metastatic/unresectable epNEC is typically platinum–etoposide chemotherapy (often extrapolated from small-cell lung cancer), with few proven targeted or immunotherapy options after progression; this trial asks whether adding upfront, biomarker-selected immune redirection can extend survival beyond chemo alone.