Abstract CT092: A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: Vaginal cancers

Abstract Background: SWOG S1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART) administered ipilimumab and nivolumab to patients with primary vaginal cancers. Methods: DART is a prospective, open-label, multicenter, multi-cohort phase II clinical trial of ipilimumab (1 mg/kg intravenously) every six weeks plus nivolumab (240 mg intravenously) every two weeks. The trial was carried out by the Early Therapeutics and Rare Cancers Committee (NCI/SWOG) and opened at >1000 sites. Cohort 33 included patients with vagina cancers only. The primary endpoint was objective response rate [ORR, confirmed complete and partial responses (CR and PR, respectively)] (RECISTv1.1), progression-free survival (PFS), and overall survival (OS); clinical benefit rate [CBR: ORR plus stable disease (SD)>6 months] and toxicity were secondary endpoints. Results: Seven evaluable patients (median age, 60 years; performance status 0-1; no prior exposure to immunotherapy) were analyzed (adenocarcinoma, N=3; squamous cell carcinoma (SCC) (N=2); small cell carcinoma and undifferentiated histology (N=1 each). The ORR was 29%: one, CR (undifferentiated) (lasting 14.8 months); one, PR (SCC) (lasting 45.2 months). The CBR was 43% (3/7 patients) (included one adenocarcinoma with 8 months SD). The 6-month PFS rate was 43%; median OS, 11.7 months. Five patients (71.4%) experienced an adverse event (AE); four, a grade 3-4 AE including one patient (14.3%) with elevated liver function tests leading to drug discontinuation. The most common AEs (any grade, at least possibly related to treatment) were cough (42.9%), fever (42.9%) and diarrhea (42.9%). Conclusion: Ipilimumab plus nivolumab in vaginal cancers resulted in an ORR of 29% and CBR of 43% including one CR, one PR and one patient with 8 months of stable disease; the longest response lasted 45.2 months. Further prospective studies exploring the role of both monotherapy and dual immunotherapy in vaginal cancers are warranted. Citation Format: Young K. Chae, Josie Czeskleba, Sandip P. Patel, Alex Menter, William Robinson, Nathaniel L. Jones, Murtuza Rampurwala, Aung Naing, Joseph M. Beck, Carolyn Moloney, Liam IL-Young Chung, Christine M. McLeod, Helen X. Chen, Elad Sharon, Sara Threlkel, Megan Othus, 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: Vaginal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr CT092.