Cemiplimab in locally advanced and/or metastatic secondary angiosarcomas (CEMangio): A phase II clinical trial.

• DOI: 10.1200/jco.2024.42.16_suppl.11513
• Publication Date: 2024-06-13T13:42:41Z
• Authors: Stefan van Ravens...; Jacco J. De Haan; Hans Gelderblom; Melissa H.S. Hill...; Richarda M. de Voer; Frank M. Speetjens; Suzanne E.J. Kaal; Minke Smits; Carla M.L.- van H...; Yvonne M.H. Versl...; Ingrid M.E. Desar
• Keywords: Microsatellite Instability

11513 Background: Angiosarcomas (AS) are rare and aggressive vascular sarcomas that can be subdivided in primary (de novo; pAS) secondary AS (sAS). Secondary arise due to DNA damaging factors like radiotherapy (RT) UV radiation or chronic lymphedema (Stewart Treves AS). Prognosis of locally advanced metastatic is very poor treatment options limited. sAS differ from pAS clinical behavior, genetic molecular background. Instead, show similarities cutaneous squamous-cell carcinoma, for which the immune checkpoint inhibitor (ICI) cemiplimab showed impressive results. The high T-cell infiltrated tumor microenvironment frequent damage response mutations indicate susceptibility ICI. Based on these characteristics anecdotical reports responses ICI associated AS, a trial was designed with sAS. Methods: In this prospective single arm multicenter phase II trial, efficacy safety 350 mg iv 3-weekly investigated patients Using Simons two-stage design, total 18 (pts) were included. outcome best overall rate (BORR) after 24 weeks treatment. outcomes include median time (mTTR), duration (mDOR), progression-free survival (mPFS), (mOS) as well translational biomarkers response. Tumor mutational burden (TMB) microsatellite instability (MSI) using “TruSight Oncology 500” (Illumina) sequencing (n = 16). samples TMB (≥10 / Megabase (Mb)), signature analyzed. Results: At cutoff date (23-Jan-24) all projected pts have been included (12 RT-sAS, 3 UV-sAS, Stewart sAS). Cemiplimab first line 10 (55.6%), second 6 (33.3%) third 2 (11.1%). Median follow-up 8.0 months. BORR at 27.8%, partial (PR) 4 (2 RT-sAS UV-sAS) 1 complete (CR) RT-sAS. One patient PR (UV-AS) developed CR. both CR ongoing. mTTR 2.6 months (range 1.2-5.4) mDOR 6.2 0.43-N/A). mPFS 4.1 (95% CI 1.2-6.4) mOS not reached. toxicity profile expected. Three stopped related (1 pt hepatitis grade 3, 4, dermatitis 2). High observed showing single-base substitution 7a, damage. highest (60 125 mut/Mb) weeks. None MSI. Results additional will available ASCO meeting. Conclusions: shows promising effectivity angiosarcomas. Clinical information: NCT04873375 .