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)

Michael J. Wagner, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA wagnermj@uw.edu.
Megan Othus, SWOG Statistical and Data Management Center/Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Sandip P. Patel, Department of Medicine, UCSD Moores Cancer Center, La Jolla, California, USA.
Chris Ryan, Department of Medicine, OHSU, Portland, Oregon, USA.
Ashish Sangal, Western Regional Medical Center, Goodyear, Arizona, USA.
Benjamin Powers, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.
G Thomas Budd, Hematology and Medical Oncology, Cleveland Clinic, Cleveland, Ohio, USA.
Adrienne I. Victor, Department of Medicine, University of Rochester, Rochester, New York, USA.
Chung-Tsen Hsueh, Loma Linda University, Loma Linda, California, USA.
Rashmi Chugh, Department of Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Suresh G. Nair MD, Lehigh Valley Health NetworkFollow
Kirsten M. Leu, Nebraska Methodist Health System, Omaha, Nebraska, USA.
Mark Agulnik, Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, California, USA.
Elad Sharon, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA.
Edward Mayerson, SWOG Statistical and Data Management Center/Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Melissa Plets, SWOG Statistical and Data Management Center/Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Charles Blanke, Department of Medicine, OHSU, Portland, Oregon, USA.
Howard Streicher, Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, Maryland, USA.
Young Kwang Chae, Department of Medicine, Northwestern University, Chicago, Illinois, USA.
Razelle Kurzrock, Department of Medicine, UCSD Moores Cancer Center, La Jolla, California, USA.

Document Type

Article

Publication Date

8-1-2021

Publication Title

Journal for immunotherapy of cancer

E-ISSN

2051-1426

Department(s)

Hematology-Medical Oncology Division

Keywords

Clinical Trials, Combination, Drug Therapy, Immunotherapy, Phase II as Topic, Sarcoma

Abstract

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

Volume

9

Issue

8

DOI

10.1136/jitc-2021-002990

PubMed ID

34380663

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