Efficacy and Safety Evaluation of Tarlatamab in Advanced Extrapulmonary Neuroendocrine Carcinoma Patients

1. study rationale Extrapulmonary neuroendocrine carcinomas (EPNECs) are rare, aggressive malignancies with poor prognosis, lacking established second-line treatments. First-line therapy, adapted from small cell lung cancer (SCLC), consists of platinum-based chemotherapy, but responses are short-lived, and salvage options offer limited benefit (response rates 10-30%, overall survival 5-7 months). Delta-like ligand 3 (DLL3) is highly expressed in EPNECs, making it a promising therapeutic target. Tarlatamab, a DLL3-targeting bispecific T cell engager (BiTE), has demonstrated durable antitumor activity in relapsed SCLC. Given its efficacy in DLL3-expressing tumors, tarlatamab may provide a novel treatment option for EPNECs. 2. Study Design This is an open-label, single-arm, multi-center, phase 2 study that will evaluate efficacy and safety of tarlatamab (AMG 757) for the treatment of subjects with extrapulmonary neuroendocrine carcinomas (EPNECs) who have progressed after 1 prior line of platinum-containing therapy. The study will be composed of 2 cohorts; cohort 1 (gastrointestinal and pancreaticobiliary NEC) and cohort 2 (genitourinary NEC). The study consists of a 21-day screening period, a treatment period, a safety follow-up (SFU) visit, and a long-term follow-up (LTFU) period. 3. The primary objective of the study is to assess the efficacy of tarlatamab based on the objective response rate (ORR) as determined by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. The primary estimand focuses on the proportion of participants achieving a partial or complete response. A secondary objective is to evaluate progression-free survival (PFS), defined as the time from treatment initiation until disease progression or death. 4. Intervention Details Participants will receive tarlatamab via intravenous (IV) infusion according to the following schedule: Cycle 1: Day 1 (C1D1): 1 mg IV over 60 minutes Day 8 (C1D8): 10 mg IV over 60 minutes Day 15 (C1D15): 10 mg IV over 60 minutes Subsequent Cycles: 10 mg IV every two weeks There is no placebo in this study.