Abstract 141TiP
Background
Angiosarcomas (AS) are rare and aggressive vascular sarcomas that can be subdivided in primary (de novo) and secondary AS. Secondary AS are frequently located in the skin, arising due to DNA damaging noxes like radiotherapy and UV radiation or due to chronic lymphedema (Stewart Treves AS). Prognosis of metastatic AS is extremely poor and treatment options are limited to chemotherapy, and the tyrosine kinase inhibitor pazopanib. Secondary AS differ from primary AS in clinical behavior, genetic and molecular background, with a more T-cell infiltrated tumor microenvironment and frequent DNA damage response mutations, indicating possible susceptibility to immune checkpoint inhibitors (ICI). Based on these tumor characteristics and anecdotical reports of responses to ICI in UV associated secondary AS, a clinical trial was designed with the ICI cemiplimab, in locally advanced or metastatic secondary AS.
Trial Design
The CEMangio study is a phase II prospective single arm multicenter clinical trial investigating the efficacy and safety of cemiplimab 350 mg iv 3-weekly in secondary AS. The trial is conducted in three specialized tertiary sarcoma centers in the Netherlands. A Simon’s two stage design is used. In the first stage, 13 patients are accrued. In case of two or more objective responses in the first stage, a total number of 18 patients will be included. Patients with locally advanced or metastatic secondary AS, in the first line of treatment, or in advanced lines of treatment are included. The primary outcome measure is to evaluate the best overall response rate (BORR) after 24 weeks of cemiplimab treatment according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1. Secondary objectives include the median time to response, duration of response, progression-free survival, and overall survival. The relationship between response to cemiplimab and tumor characteristics, including MYC status, tumor mutational burden, PD-L1 expression and tumor infiltrating lymphocytes, is investigated. Enrollment is ongoing, 17 out of 18 projected patients have been included.
Clinical trial identification
NCT04873375.
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Radboud University Medical Center Genzyme Europe B.V.
Disclosure
All authors have declared no conflicts of interest.