SWOG/NCI Phase II Dual Anti–CTLA-4/PD-1 Blockade in Rare Tumors: Nonepithelial Ovarian Cancer
Young Kwang Chae, Megan Othus, Sandip Pravin Patel, Kelly J. Wilkinson, Emily M. Whitman-Purves, Jayanthi Lea, John M. Schallenkamp, Nabil Adra, Leonard J. Appleman, Mitchell Alden, Jessica Thomes Pepin, John Ellerton, Andrew Poklepovic, Adam Walter, Murtuza Rampurwala, William R. Robinson, Hye Sung Kim, Liam Il‐Young Chung, Christine M. McLeod, G. López, Helen X. Chen, Elad Sharon, Howard Streicher, Christopher W. Ryan, Charles D. Blanke, Razelle Kurzrock
Abstract
PURPOSE: The role of dual checkpoint inhibition (ipilimumab at 1 mg/kg intravenously every 6 weeks and nivolumab at 240 mg intravenously every 2 weeks) in advanced rare/ultrarare nonepithelial ovarian cancers is yet to be explored. PATIENTS AND METHODS: Dual anti-CTLA-4 and anti-PD-1 blockade in rare tumor is a prospective, multicenter (1,016 US sites), multicohort, single-arm phase II trial conducted through the Early Therapeutics and Rare Cancer SWOG/NCI Committee, assessing ipilimumab (anti-CTLA-4; 1 mg/kg every 6 weeks) and nivolumab (anti-PD-1; 240 mg every 2 weeks) in adults with advanced nonepithelial ovarian cancers who lack beneficial standard therapy. The primary outcome was overall response rate [ORR; complete response (CR)/partial response (PR)]; secondary outcomes were progression-free survival (PFS), overall survival, clinical benefit rate [stable disease (SD) ≥6 months plus ORR], and toxicity. RESULTS: Seventeen patients (median age: 64; number of prior therapies ranged from 0 to 8 with no immunotherapy exposure; eight granulosa, six carcinosarcomas, one Sertoli-Leydig, one yolk sac, and one Wolffian) were evaluated. In granulosa cell tumors, ORR was 25% (n = 2/8; one CR and one PR) and clinical benefit rate was 50% (n = 4/8); PFS was 58.3 (CR), 50.7+ (PR), 30.4 (SD), and 8.7 (SD) months. Median PFS was 3.5 months [95% confidence interval, 1.7-11.2 months]; median overall survival was 42.5 months (95% confidence interval, 10.1 months-not reached). One Sertoli-Leydig cell tumor showed a 22% regression (PFS, 11.2 months). Carcinosarcomas had no response. Three participants (18%) discontinued treatment due to grade 3 to grade 4 adverse events. CONCLUSIONS: Ipilimumab-nivolumab shows activity in treatment-refractory granulosa cell tumors, with 25% (n = 2/8) of patients experiencing either CR or PR lasting more than 4 years.