Ipilimumab Plus Nivolumab Promising for Patients with Metastatic or Unresectable Angiosarcoma

A prospective, open-label, multicenter, phase 2 trial of ipilimumab (Yervoy) plus nivolumab (Opdivo) for patients with metastatic or unresectable angiosarcoma indicated that the combination was well-tolerated, warranting further investigation of the combination for this patient population.¹

This study was part of a path-breaking clinical trial called DART, short for Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors.² Launched in 2017, DART uses an innovative “basket” design to test the effectiveness of the ipilimumab and nivolumab combination in a variety of rare tumor types. Through DART, the drug combination has completed testing in 36 cohorts of rare cancer patients, with another 12 cohorts still taking the drugs, and 4 cohorts temporarily closed for data analysis.

The results observed in patients with metastatic or unresectable angiosarcoma, shared in a virtual oral presentation at The Society for Immunotherapy of Cancer’s (SITC) 35th Anniversary Annual Meeting, demonstrated an objective response rate (ORR) of 25% in angiosarcoma regardless of primary site, with 3 of 5 patients with cutaneous tumors of the scalp or face responding. Importantly, this study is the first to provide evidence that immunotherapies can treat angiosarcoma.

“These results open a new way to treat angiosarcoma – with immunotherapy,” Michael Wagner, MD, of the University of Washington, the Fred Hutchinson Cancer Research Center, and the Seattle Cancer Care Alliance, said in a press release. “At [SWOG Cancer Research Network, a cancer clinical trials group funded by the National Cancer Institute’s (NCI) Division of Cancer Diagnosis and Treatment], we’re planning a larger follow-up study to see if this combination can work as a first line of treatment.”

In this ongoing study, participants with metastatic or unresectable angiosarcoma were administered 1 mg/kg of ipilimumab intravenously (IV) every 6 weeks plus 240 mg of nivolumab by IV every 2 weeks. The primary end point is ORR as assessed by RECIST v1.1, including measurable cutaneous disease that can be followed by photography. Key secondary end points include progression-free survival (PFS), overall survival (OS), stable disease at 6 months, and toxicity.

Of note, a two-stage design was used with 6 patients in the first stage and an additional 10 patients in the second stage for a total of 16 patients with angiosarcoma enrolled. Median age was 68 years (range, 25-81 years). Median number of prior lines of therapy was 2 (range, 0-5).

At the data cutoff, 9 patients had cutaneous primary tumors of any cutaneous site and 7 had non-cutaneous primary tumors. The ORR for all patients was 25%. Moreover, subgroup analysis also revealed that 60% of patients with primary cutaneous tumors of the scalp or face had a confirmed objective response. The 6-month PFS was 38%.

Regarding safety, 75% of patients experienced an adverse event (AE), and 25% experienced a grade 3 or 4 AE. Further 68.8% experienced an immune related AE (irAE), and 2 (12.5%) developed grade 3 or 4 irAEs.

The grade 3 or 4 irAEs observed were alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increase, as well as diarrhea. There were no grade 5 toxicities reported.

References:

1. Wagner M, Othus M, Patel S, et al. 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). Presented at The Society for Immunotherapy of Cancer’s (SITC) 35th Anniversary Annual Meeting. Abstract #: 795.

2. Rare Angiosarcomas Respond to Immunotherapy [news release]. SWOG Cancer Research Network. Published November 13, 2020. Accessed November 16, 2020. https://www.swog.org/news-events/news/2020/11/13/rare-angiosarcomas-respond-immumotherapy