This phase II clinical trial evaluates the efficacy, safety and tolerability of Obrixtamig in addition to standard of care chemotherapy (Platinum/Etoposide) in LCNEC.

Inclusion Criteria: (main criteria)

1. Patient has provided written informed consent and is able to consent
2. Patients with pulmonary large-cell neuroendocrine carcinoma (LCNEC) defined by local histology and immunohistochemistry; patients with mixed histology are eligible if LCNEC is the predominant histology, i.e. ≥50%
3. Patients with locally advanced or metastatic disease without curative treatment options
4. All patients must have received one, but not more than one, cycle of platinum/etoposide chemotherapy with or without immune checkpoint inhibitor (standard-of-care; SoC). Other than that, patients must be previously untreated with systemic therapy.
5. Measurable disease according to RECIST v1.11

Exclusion Criteria: (main criteria)

1. Symptomatic brain metastases (Patients with asymptomatic brain metastases are allowed provided they are clinically stable, receiving no or a stable dose of anticonvulsants without steroid treatment for at least 3 weeks.)
2. Known leptomeningeal disease
3. Any prior systemic treatment for metastatic disease, except for one cycle of SoC as described under inclusion criteria
4. Previous treatment with obrixtamig or any anti-DLL3 compound including T-cell engagers and antibody-drug conjugates