Neuroendocrine neoplasms (NENs) comprise a heterogeneous family of neoplasms arising from the neuroendocrine cells localized in endocrine glands or from the diffuse neuroendocrine cells such as in the digestive or lung tract.
Treatment for gastroenteropancreatic neuroendocrine tumors (GEP-NEC) is primarily based on chemotherapy regimens, primarily platinum, which achieve limited benefit and a median overall survival of approximately 12 months.
Currently, new treatments that activate the immune system to stimulate antitumor responses and prolong survival in patients with NECs are being investigated.
Given the high levels of DLL3 expression on the cell surface of neuroendocrine tumor cells and its minimal, primarily cytoplasmic, localization in normal tissues, DLL3 is a promising target for the development of T-cell-directed therapies in NECs. Tarlatamab is a HLE BiTE molecule that combines the binding specificities for DLL3 and CD3, which could activate the immune system to fight NEC cells.
The main hypothesis is that treatment with tarlatamab, a bispecific anti-DLL3 and anti-CD3 conjugate, either as a single agent or in combination with standard second-line chemotherapy (FOLFIRI) scheme could be an effective treatment option for patients with advanced neuroendocrine carcinomas of the digestive system or unknown primary origin.
Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written informed consent.
Patient is ≥ 18 years of age.
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
Histologically confirmed neuroendocrine carcinomas (NECs) of the digestive system or unknown primary origin.
Paraganglioma, adrenal, thyroid parathyroid or pituitary endocrine tumors,
Large or small cell lung neuroendocrine carcinoma of the lung,
Neuroendocrine tumors (NETs) of the gastrointestinal tract or unknown origin (i.e. well differentiated tumors)
Malignancy (other than in situ) treated with curative intent and with no known active disease present for 2 years before first dose of tarlatamab and felt to be at low risk for recurrence by the treating physician.
Grupo Espanol de Tumores Neuroendocrinos
Lead sponsor
Amgen
Collaborator