Multicenter phase II trial (SWOG S1609, cohort 51) of ipilimumab and nivolumab in metastatic or unresectable angiosarcoma: a substudy of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART)

• DOI: 10.1136/jitc-2021-002990
• Publication Date: 2021-08-12T00:25:37Z
• Authors: Michael J Wagner; Megan Othus; Sandip P Patel; Chris Ryan; Ashish Sangal; Benjamin Powers; G Thomas Budd; Adrienne I Victor; Chung-Tsen Hsueh; Rashmi Chugh; Suresh Nair; Kirsten M Leu; Mark Agulnik; Elad Sharon; Edward Mayerson; Melissa Plets; Charles Blanke; Howard Streicher; Young Kwang Chae; Razelle Kurzrock
• Keywords: Clinical endpoint

Purpose Angiosarcoma is a rare aggressive endothelial cell cancer with high mortality. Isolated reports suggest immune checkpoint inhibition efficacy in angiosarcoma, but no prospective studies have been published. We report results for angiosarcoma treated ipilimumab and nivolumab as cohort of an ongoing study. Methods This prospective, open-label, multicenter phase II clinical trial (1 mg/kg intravenously every 6 weeks) plus (240 mg 2 metastatic or unresectable angiosarcoma. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints include progression-free (PFS) overall survival, toxicity. A two-stage design used. Results Overall, there were 16 evaluable patients. Median age 68 years (range, 25–81); median number prior lines therapy, 2. Nine patients had cutaneous seven non-cutaneous primary tumors. ORR 25% (4/16). Sixty cent (3/5) scalp face tumors attained confirmed response. Six-month PFS 38%. Altogether, 75% experienced adverse event (AE) (at least possibly related to drug) (25% grade 3–4 AE); 68.8%, immune-related AE (irAE) (2 (12.5%), 3 4 irAEs (alanine aminotransferase/aspartate aminotransferase increase diarrhea)). There 5 toxicities. One whom tumor mutation burden (TMB) assessed showed TMB (24 mutations/mb); that patient achieved partial (PR). Two three PDL1 immunohistochemistry expression; one PR. Conclusion The combination demonstrated five the responding. Ipilimumab warrant further investigation Trial registration NCT02834013 .