A phase II trial of pembrolizumab in combination with cisplatin or carboplatin and etoposide in chemotherapy naive patients with metastatic or unresectable high-grade gastroenteropanncreatic or lung neuroendocrine carcinoma.

Abstract

TPS635 Background: Combination chemotherapy (CTx) is the mainstay of treatment for patients with advanced high-grade gastroenteropancreatic neuroendocrine carcinoma (GEPNECs) and large cell neuroendocrine carcinomas (LCNECs) of the lung. Pembrolizumab (PEM) is a humanized antibody to the programmed cell death receptor (PD-1), which blocks the interaction with its cognate ligands, PD-L1 and PD-L2. PEM blocks the protective mechanism of cancer cells and allows the immune system to destroy them. Combination Ctx and immunotherapy has shown efficacy in other malignancies including small cell lung cancer. The purpose of this study is to test the efficacy, safety, and tolerability of combination CTx with PEM in patients with high-grade GEPNEC or LCNEC of the lung who are CTx naïve. Methods: This is an open label, phase II, single institution, multi-site trial using PEM in combination with either cisplatin or carboplatin and etoposide in patients with high grade GEPNECs or LCNEC of the lung who are CTx naïve. Patients with a histologic diagnosis of a GEPNECs with a Ki-67 of 55% or higher or a LCNEC of the lung will be eligible. Patients must be metastatic or unresectable; chemotherapy naïve; have at least one measurable lesion per RECIST 1.1, have an ECOG performance score of 0-1; and have a predicted life expectancy > 3 months. Approximately 36 GEPNEC and 6 LCNEC of the lung patients will be enrolled. Patients will receive PEM 200mg IV in combination with cisplatin 80 mg/m2 or carboplatin AUC 6 on day 1 and etoposide 100mg/m2 on days 1-3 of a 21-day cycle. Tumor response will be assessed by CT scan every 6 weeks using RECIST 1.1. Those patients who have responsive or stable disease after 4-6 cycles of platinum-based CTx will move to maintenance PEM every 3 weeks for up to 2 years. The primary endpoint will be progression free survival. Results: This study is open to enrollment. Clinical trial information: NCT03901378.