P2.12-05 A Phase II Trial of Pembrolizumab With Chemotherapy in Metastatic or Unresectable High Grade Neuroendocrine Carcinoma

Combination chemotherapy is the mainstay of treatment for patients with high-grade gastroenteropancreatic neuroendocrine carcinoma (GEPNECs) and neuroendocrine carcinomas (NECs) of the lung. Pembrolizumab, a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb), has high specificity for binding to the programmed cell death 1 (PD-1) receptor thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). In combination with chemotherapy, pembrolizumab blocks the protective mechanism of cancer cells and allows the immune system to destroy them. Combination chemotherapy and pembrolizumab was recently FDA approved and ongoing trials are utilizing this or similar combinations with data demonstrating a promising safety profile. The purpose of this study is to test the efficacy, safety, and tolerability of combination chemotherapy with pembrolizumab in patients with high-grade neuroendocrine carcinomas of the gastroenteropancreatic system or lung who are chemotherapy naïve. This is an open label, phase II, single institution, multi-site trial using pembrolizumab in combination with either cisplatin or carboplatin and etoposide in patients with high grade neuroendocrine carcinomas of the gastroenteropancreatic system or lung who are chemotherapy naïve. Patients with a histologic diagnosis of a GEPNECs with a Ki-67 of 55% or higher or a large cell NEC of the lung will be eligible for inclusion in this study. Subjects must be deemed unresectable and have not undergone prior chemotherapy for metastatic disease. Patients must also have at least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, an Eastern Cooperative Oncology Group (ECOG) performance score of 0-1, and a predicted life expectancy >3 months. Approximately 36 GEPNEC patients will be enrolled with an exploratory LCNEC of the lung cohort of approximately 6 patients. Patients will receive pembrolizumab 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 computerized tomography scan every 6 weeks calculated with the first CT within 7 days of initiation of treatment. RECIST 1.1 will be used for treatment decisions until there is evidence of progressive disease (PD). Those patients who have responsive or stable disease after 4-6 cycles of platinum-based chemotherapy will move to maintenance pembrolizumab every 3 weeks. The primary endpoint will be progression free survival (PFS) per RECIST 1.1. ClinicalTrials.gov Identifier: NCT03901378 Section not applicable Section not applicable