Abstract CT163: A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the small cell carcinoma of the ovary, hypercalcemic type cohort
Authors: Chae Young Kwang , Othus Megan , Patel Sandip P. , Aljumaily Raid , Win Khine Z. , Pejovic Tanya , Thomas Sajeve S. , Robinson William R. , Chung Liam Il-Young , McLeod Christine M. , Chen Helen X. , Sharon Elad , Streicher Howard , Ryan Christopher W. , Blanke Charles D. , Kurzrock Razelle 
Published: April 2023

Abstract
Background: Dual checkpoint inhibition with Anti-PD-1 and anti-CTLA4 checkpoint inhibitors have shown to be efficacious in many malignancies, but its potential role in various rare solid cancers is yet to be established. Small cell ovarian carcinoma, hypercalcemic type (SCCOHT) is a rare tumor characterized by loss of SMARC 2/4 function and so presents a novel paradigm for the treatment of SWI/SNF pathway deficient tumors (Petar Jelinic et al., 2018; Marc Tischkowitz et al., 2020). This study presents the first results of ipilimumab and nivolumab used in the SCCOHT cohort (#49) of the SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial.
Methods: DART is a prospective, open-label, multicenter/multi-cohort phase 2 clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks). The primary endpoint includes objective response rate (ORR) (RECIST v1.1) (confirmed complete (CR) and partial responses (PR)). Secondary endpoints include progression-free survival (PFS), overall survival (OS), stable disease (SD) &gt;6 months, and toxicity.
Results: Five evaluable patients (median age 30) with SCCOHT were analyzed. Objective response rate was 20% (1 CR with 100% regression). The patient with CR has a duration of response (DoR) and OS of 35+ months. Another patient, showed unconfirmed PR with 81% regression (DoR 4 months), this patient went on to have confirmed iCR (CR confirmed by iRECIST) at around 24 months and has OS of 38+ months. At 12 months, 3 patients remain alive and 1 patient remains progression free; overall median PFS was 1.8 months (1.0-∞); median OS was 24 months (4.5-∞). The most common adverse events were fatigue, nausea, pruritus, dry mouth, maculo-papular rash and aspartate aminotransferase elevation (50%, n=2, respectively). There were two incidents (33.3%) of grade 3-4 adverse events. None of the adverse events led to discontinuation. There were no grade 5 adverse events.
Conclusion: Ipilimumab plus nivolumab in five patients with the ultra-rare small cell ovarian carcinoma (hypercalcemic type) resulted in one CR durable at 35+ months and one unconfirmed PR with 81% regression. This is the first prospective study demonstrating efficacy of nivolumab and ipilimumab in this rare disease. Correlative studies to determine response and resistance markers are ongoing. Expanded prospective studies in small cell ovarian histologies are needed.
Citation Format: Young Kwang Chae, Megan Othus, Sandip P. Patel, Raid Aljumaily, Khine Z. Win, Tanya Pejovic, Sajeve S. Thomas, William R. Robinson, Liam Il-Young Chung, Christine M. McLeod, Helen X. Chen, Elad Sharon, Howard Streicher, Christopher W. Ryan, Charles D. Blanke, Razelle Kurzrock. A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the small cell carcinoma of the ovary, hypercalcemic type cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT163.