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.
Parallel
Tarlatamab
DrugTarlatamab as a standalone treatment through intravenous infusion at 10 mg dose every 14 days (i.e. 2 weeks)
standard of care second-line chemotherapy (FOLFIRI)
DrugFOLFIRI:: irinotecan intravenously 180 mg/m2 on day 1, followed by 400 mg/m2 folinic acid or 200 mg/m² levofolinate in a 2-h infusion, a 10-min bolus of 400 mg/m2 5-FU, and 2400 mg/m2 5-FU over 46 hours; every 14 days).
Progression-free Survival (PFS) rate
The percentage of patients without progression as defined by RECIST V1.1 criteria or death. PFS rate will be calculated for each treatment arm separately once 38 PFS events are reported in the first 54 patients included (27 per treatment arm). Patients alive and free of events at the date of the analysis will be censored at their last known tumor assessment. Patients who start a new treatment line without progression will be censored on the date of first dose of the subsequent anticancer treatment.
Overall Survival (OS) rate at 12-months
Defined as the percentage of patients alive after 12 months from the first dose of study treatment. OS will consider death from any cause as an event. Patients alive and free of events at the date of the analysis will be censored at their last known contact. OS will be calculated for each treatment arm separately. We will assess the median OS, estimated by Kaplan-Meier. Patients alive and free of events at the date of the analysis will be censored at their last known contact. Survival will be assessed by recording patient status at each visit according to protocol. Long term follow up to be performed at least every 6 months
Objective response rate (ORR)
Assessed by the investigator through imaging follow-up (CT scan/MRI) using RECIST 1.1. This will be considered as the percentage/proportion of patients with complete response (CR) or partial response (PR) as their overall best response throughout the study period. Objective responses will be assessed locally by the investigator according to RECIST, version 1, and indicating the change in size of tumors as compared with baseline, at the first dose of study treatment.
Disease control rate (DCR)
Assessed locally by the investigator through imaging follow-up (CT scan/MRI) using RECIST 1.1. DCR will include the percentage/proportion of patients with CR, PR, or SD (maintained \> 4 months) as their overall best response throughout the study period. The DCR will be estimated by binomial proportion, dividing the number of patients with CR, PR or SD for at least 4 months for DCR by the total number of patients studied in the population. The corresponding exact 2-sided 95% CIs will be provided. Changes in tumor size from baseline will be calculated and displayed graphically, where appropriate
Duration of response (DoR)
Time from first response (CR or PR), according to ORR definition for the trial, to the date of the documented PD as determined using RECIST 1.1 criteria or death due to any cause, whichever occurs first. Those patients with response and without PD or death event will be censored on the date of their last tumor assessment. DoR will be summarized using Kaplan-Meier method and displayed graphically, where appropriate. The mean, median DoR and 95% CIs will be provided.
Patient reported health-related quality of life (HRQoL)
Assessed through the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30), version 3. Summary statistics \[mean (and SE), median, range and 95% CI\] of absolute scores will be reported for all of the subscales of the EORTC QLQ-C30 questionnaire. The mean change of absolute scores from baseline (and 95% CI) will also be assessed. Line charts depicting the means and mean changes of items and subscales over time will be provided. The EORTC QLQ-C30 is a questionnaire used to assess the quality of life in cancer patients. It consists of 15 scales, including 5 functional scales, 3 symptom scales, and 9 multi-item and single-item scales for measuring symptoms and global health status. Scores range from 0 to 100, with higher scores indicating better functioning or higher quality of life for functional scales and global health status, but higher scores indicate a higher level of symptoms for symptom scales
Click on the lead sponsor to view all of their trials.
Grupo Espanol de Tumores Neuroendocrinos
Lead sponsor
Amgen
Collaborator
