Background: Since their first approval in 2011 for metastatic melanoma, checkpoint inhibitors have been successfully applied to multiple tumor types. To date, the potential role for these treatments in rare solid tumors has not been well studied. We report the results of three salivary gland neoplasm cohorts of SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) trial.

Methods: We performed a prospective, open-label, multicenter phase 2 clinical trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks) in multiple tumor types. Here, we report the results found in three salivary gland neoplasm cohorts that include patients with salivary gland tumor types arising in major salivary glands (cohort 2), other sites of origin (cohort 3) and adenoid cystic carcinomas of any site (cohort 34). Primary endpoints included overall response rate (ORR) (RECIST v1.1) (complete response (CR) and partial responses (PR)); secondary endpoints included progression-free survival (PFS) and overall survival (OS), stable disease >6 months, and toxicity.

Results: Twenty six patients with adenoid cystic salivary gland tumors and thirty five patients with other histologic subtypes of salivary gland neoplasm received therapy. The most common site of origin was the parotid (35%; N=9 in the adenoid cystic group and 54%; N=19 in the remaining histologies). The overall ORR in the adenoid cystic group was 4% (CR, 0%; PR, 4%, N= 1) and the median PFS was 4.4 months. 6 month OS was 84% and median OS was 12 months. In the remaining histologic subtypes the ORR was 9% (CR, 0%; PR, 9%, N=3) and the median PFS was 4.6 months. 6-month OS was 89%, median OS was not reached. The most common toxicities were fatigue (39%) and diarrhea (26%), with diarrhea (8%) as the most common grade 3-5 immune-related adverse event.

Conclusions: In salivary gland tumors, combination therapy with ipilimumab plus nivolumab resulted in a 4% ORR in adenoid cystic carcinoma and 9% in other histologies combined.

Citation Format: Young Kwang Chae, Megan Othus, Sandip Pravin Patel, James P. Ohr, Francis P. Worden, Jennifer M. Suga, Aung Naing, Sarah E. Fenton, Hyunseok Kang, Sewan Gurung, Christine M. McLeod, Francis J. Giles, Helen X. Chen, Elad Sharon, Edward Mayerson, Melissa Plets, Christopher 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 salivary gland tumor cohort [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3418.