Abstract CT039: A Phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) S1609: The neuroendocrine cohort
Authors: Patel Sandip Pravin , Othus Megan , Chae Young Kwang , Giles Francis , Hansel Donna , Singh Preet , Fontaine Annette , Shah Manisha , Kasi Anup , Baghdadi Tareq Al , Matrana Marc , Gatalica Zoran , Korn W. Michael , Hayward Jourdain , MMcLeod Christine , Chen Helen X. , Sharon Elad , Mayerson Edward , Ryan Christopher W. , Plets Melissa , Blanke Charles D. , Kurzrock Razelle 
Published: August 2019

Abstract
Background: Immune checkpoint blockade, in particular anti-CTLA-4 and anti-PD-1-directed approaches, have improved outcomes in various tumor types. However, little is known about the efficacy of these agents in metastatic rare solid tumors. We report here the results of the neuroendocrine cohort of SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART).
Methods: We performed a prospective, open-label, multicenter phase 2 clinical trial of ipilimumab (1mg/kg q6 weeks) plus nivolumab (240mg intravenously every 2 weeks) across multiple cohorts of rare tumors, with the neuroendocrine cohort reported here. Pancreatic neuroendocrine tumors are currently being accrued to a separate cohort of S1609. The primary endpoint was overall response rate (ORR) by RECIST v1.1 (complete (CR) and partial responses (PR)); secondary endpoints included progression-free (PFS) and, overall survival (OS), stable disease (SD) &gt;6 months, and toxicity.
Results: Thirty-three eligible patients received therapy; 58% (N= 19) had high-grade disease; most common sites were gastrointestinal (non-pancreatic) (45%; N = 15) and lung (18%; N = 6). Patients had received a median of 2 lines of prior therapy. The overall response rate was 24% (CR, 3%; PR, 21%). Patients with high-grade neuroendocrine cancer had a 42% (8 of 19 patients) response rate vs. 0% in low/intermediate grade tumors (0/14 patients; p = 0.01). The 6-month PFS was 30%; median OS was 11 months. The most common toxicities were fatigue (30% of patients) and nausea (27%). Alanine aminotransferase (ALT) elevation (9%) was the most common grade 3-4 irAE, with no grade 5 toxicities.
Conclusions: Ipilimumab plus nivolumab was well tolerated with a 42% ORR in patients with high-grade neuroendocrine cancer, regardless of primary site. Further investigation of this combination is warranted.
Best Response Summary in 33 Patients with Neuroendocrine CancerResponse TypeAll Patients (n=33)High grade (n=19)Low/Intermediate grade (n=14)Complete Response (CR)1 (3%)1 (5%)0Partial Response (PR)7 (21%)7 (37%)0Stable Disease (SD)&gt;6months2 (6%)02 (14%)SD11 (33%)3 (17%)8 (57%)Progressive Disease (PD)12 (36%)8 (42%)4 (29%)CR+PR8 (24%)8 (42%)0CR+PR+SD&gt;6mo10 (30%)8 (42%)2 (14%)
Citation Format: Sandip Pravin Patel, Megan Othus, Young Kwang Chae, Francis Giles, Donna Hansel, Preet Singh, Annette Fontaine, Manisha Shah, Anup Kasi, Tareq Al Baghdadi, Marc Matrana, Zoran Gatalica, W. Michael Korn, Jourdain Hayward, Christine MMcLeod, Helen X. Chen, Elad Sharon, Edward Mayerson, Christopher W. Ryan, Melissa Plets, Charles D. Blanke, Razelle Kurzrock. A Phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) S1609: The neuroendocrine cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT039.