Phase II study of pembrolizumab-based therapy in previously treated extrapulmonary poorly differentiated neuroendocrine carcinomas: Results of Part A (pembrolizumab alone).

363 Background: Immune checkpoint inhibitor (CPI) efficacy has not been established in extrapulmonary poorly-differentiated neuroendocrine carcinomas (EP-PDNECs). In small cell lung cancer, promising antitumor activity of CPI led to accelerated approval of nivolumab in 8/2018. We investigated the efficacy and safety of pembrolizumab (PEM)-based therapy in biomarker-unselected EP-PDNECs. Methods: Open label, multicenter, phase 2 study of PEM-based therapy in patients (pts) with EP-PDNECs, excluding Merkel cell carcinoma and well differentiated grade 3 NET, with progression on first-line systemic therapy, ECOG 0-1, and adequate hepatic and renal function. Enrollment via an adaptive Simon’s 2-stage design. Plan for 14 pts treated with PEM alone (Part A Stage 1) 200 mg IV every 3 weeks. If > 2 of 14 pts respond by week 18, then 21 additional pts enroll in Part A Stage 2, corresponding to H 0 10% vs. H 1 26% response rate (RR) at type I error 0.05 with power 80%. Otherwise study proceeds to Part B: PEM plus chemotherapy (dealer's choice of weekly irinotecan or paclitaxel). Primary endpoint is objective RR (ORR) by RECIST 1.1. Secondary endpoints include safety, overall survival, and progression-free survival (PFS). Serial blood samples and baseline tumor biopsies required in all pts for future biomarker studies. Results: Preliminary data from Part A Stage 1 are available. Of 14 pts enrolled, male/female 9/5; median age 63; 1 large cell, 11 small cell, 2 NOS. Primary site of disease: GI 43%, GU 29%, and other 29%. Median Ki67 80% (available for 9 pts). Best response: CR (1), PR (0), SD (2), PD (10), unevaluable (1; early death from sepsis) for ORR 7%. Median PFS was 58 days. Six (43%) pts went off study for early PD or clinical deterioration before first scheduled scan at 9 weeks. PEM was well tolerated with no grade 3-5 AEs attributed to therapy. At last follow up, 9 (64%) pts were alive with 1 pt still on treatment after 19 cycles. Conclusions: PEM monotherapy was not effective in this pretreated, biomarker-unselected population of EP-PDNECs arising in different organs. Part B (PEM plus chemotherapy) enrollment is ongoing. Biomarker studies are planned (Parts A/B). Clinical trial information: NCT03136055.