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795 A 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)
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  1. Michael Wagner1,
  2. Megan Othus2,
  3. Sandip Patel3,
  4. Christopher Ryan4,
  5. Ashish Sangal5,
  6. Benjamin Powers6,
  7. George Budd7,
  8. Adrienne Victor8,
  9. Chung-Tsen Hsueh9,
  10. Rashmi Chugh10,
  11. Suresh Nair11,
  12. Kirsten Leu12,
  13. Mark Agulnik13,
  14. Elad Sharon14,
  15. Edward Mayerson2,
  16. Melissa Plets2,
  17. Charles Blanke15,
  18. Howard Streicher14,
  19. Young Kwang Chae13 and
  20. Razelle Kurzrock3
  1. 1University of Washington, Seattle, WA, USA
  2. 2SWOG/FHCRC, Seattle, WA, USA
  3. 3UCSD Moores Cancer Center, La Jolla, CA, USA
  4. 4OHSU, Portland, OR, USA
  5. 5CTCA at Western Regional Medical Center, Phoenix, AZ, USA
  6. 6Kansas MU-NCORP, Overland Park, KS, USA
  7. 7Cleveland Clinic, Cleveland, OH, USA
  8. 8University of Rochester, Rochester, NY, USA
  9. 9Loma Linda University, Loma Linda, CA, USA
  10. 10University of Michigan, Ann Arbor, MI, USA
  11. 11Michigan CRC NCORP, Allentown, PA, USA
  12. 12Nebraska Methodist Hospital, Omaha, NE, USA
  13. 13Northwestern University, Chicago, IL, USA
  14. 14Cancer Therapy Evaluation Program (CTEP), Bethesda, MD, USA
  15. 15SWOG Group Chair’s Office, OHSU, Portland, OR, USA
  • Journal for ImmunoTherapy of Cancer (JITC) preprint. The copyright holder for this preprint is the author/funder, who has granted JITC permission to display the preprint. All rights reserved. No reuse allowed without permission.

  • Until the paper has been able to undergo proper copyediting, typesetting, and author proofing, readers should be aware that the specific preprint information below may contain errors and has not been finalized by authors.

Abstract

Background Angiosarcoma is a rare cancer of endothelial cells that can be aggressive and carries a high mortality. A subset of angiosarcomas are characterized by high tumor mutational burden (TMB) and UV light exposure DNA mutational signature. Isolated case reports have suggested clinical efficacy of immune checkpoint blockade in angiosarcoma; no prospective studies of immune checkpoint inhibition in angiosarcoma have been reported. We report efficacy analysis results for patients with advanced or unresectable angiosarcoma treated with ipilimumab and nivolumab as a cohort of an ongoing phase II study for rare cancers (NCT02834013).

Methods This is a prospective, open-label, multicenter phase II clinical trial of ipilimumab (1mg/kg IV q6weeks) plus nivolumab (240mg IV q2weeks) for patients with metastatic or unresectable angiosarcoma. Primary endpoint is objective response rate as assessed by RECIST v1.1, including measurable cutaneous disease that can be followed by photography. Secondary endpoints include PFS, OS, stable disease at six months, and toxicity. A two-stage design is used with six patients in the first stage and an additional ten patients in the second stage.

Results At data cutoff, 16 patients with angiosarcoma were enrolled. Median age was 68 years (25-81 years). Median number of prior lines of therapy was 2 (0-5). 9 patients had cutaneous primary tumors of any cutaneous site, 7 had non-cutaneous primary tumors. ORR for all patients was 25% (4/16, table 1, figure 1). Subgroup analysis revealed that 60% (3/5) of patients with primary cutaneous tumors of the scalp or face had a confirmed objective response. 6-month PFS was 38%. 75% of patients experienced an adverse event (AE), and 25% experienced a grade 3-4 AE. 68.8% experienced an immune related AE (irAE), and 2 (12.5%) developed grade 3 or 4 irAEs. Grade 3-4 irAEs were ALT and AST increase and diarrhea. There were no grade 5 toxicities.

Conclusions The combination of ipilimumab and nivolumab was well tolerated and had an ORR of 25% in angiosarcoma regardless of primary site, with 3 of 5 patients with cutaneous tumors of the scalp or face responding. Ipilimumab and nivolumab warrant further investigation in angiosarcoma.

Acknowledgements Funding: National Institutes of Health/National Cancer Institute grant awards CA180888, CA180819, CA180868; and in part by Bristol-Myers Squibb Company

Trial Registration NCT02834013

Ethics Approval This study was approved by the NCI CIRB.

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