eligibility_summary
Eligible: unresectable advanced/metastatic SCLC, LCNEC, or EP-NEC (mixed if ≥50% NEC), DLL3+ grade 3 NET (Ki-67 ≥55%) allowed, progressed after SOC or lack options. Parts C/D include 1L/2L cohorts for CE, paclitaxel, or CE+atezolizumab. Must provide FFPE tissue, ECOG 0–1, adequate organs. Exclude: NSCLC-transformed NEC, pregnancy/poor contraception, autoimmune/immunosuppression, recent immunostims/antibiotics, ≥G3 irAEs, active brain mets, major cardiac disease, Part D hypercalcemia/CV, recent hemolysis, ≥G3 neuropathy, warfarin.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Trial: NCT05652686 (SKYBRIDGE). Drug/interventions and mechanisms: • Peluntamig (PT217): bispecific antibody targeting DLL3 (tumor-associated Notch ligand on neuroendocrine carcinomas) and CD47 (innate immune “don’t‑eat‑me” signal). Mechanism: binds DLL3+ tumor cells while blocking CD47–SIRPα, enhancing macrophage-mediated phagocytosis and Fc effector functions (ADCP/ADCC), potentially priming T‑cell responses. • Carboplatin: platinum DNA crosslinker (cytotoxic). • Etoposide: topoisomerase II inhibitor (cytotoxic). • Paclitaxel: microtubule stabilizer (cytotoxic). • Atezolizumab: anti–PD‑L1 immune checkpoint inhibitor restoring T‑cell activity. Cells/pathways targeted: • DLL3-expressing neuroendocrine carcinoma cells (SCLC, LCNEC, NEPC, GEP‑NEC, EP‑NEC). • CD47–SIRPα macrophage checkpoint (innate immunity). • PD‑1/PD‑L1 axis (adaptive T‑cell response). • DNA replication/repair and microtubules in proliferating tumor cells.