Data from Cemiplimab in Locally Advanced or Metastatic Secondary Angiosarcomas (CEMangio): A Phase II Clinical Trial and Biomarker Analyses

<div>AbstractPurpose:<p>Angiosarcomas (AS) are rare vascular sarcomas. Secondary AS (sAS) arise from DNA-damaging factors such as radiotherapy and UV radiation (UV-AS) or due to chronic lymphedema. The prognosis for advanced AS is poor, with limited treatment options. Immune checkpoint inhibition is not approved for AS, but high intratumoral T-cell density and frequent mutations in sAS may support efficacy.</p>Patients and Methods:<p>This prospective, single-arm, multicenter phase II trial assessed the efficacy and safety of cemiplimab (350 mg, intravenously every 3 weeks) in patients with locally advanced or metastatic sAS using a Simon’s two-stage design. The primary outcome was the best overall response rate within 24 weeks of treatment. Secondary outcomes included time to response, duration of response, progression-free survival, overall survival, and predictive biomarkers for treatment response.</p>Results:<p>Eighteen patients (12 with AS from radiotherapy, 3 with UV-AS, and 3 with AS due to chronic lymphedema) were treated with cemiplimab. The best overall response rate was 27.8% (4 partial responses, 1 complete response), with a time to response of 2.6 months and a duration of response of 6.9 months. The median progression-free survival was 3.7 months, and the median overall survival was 13.1 months. Grade ≥3 immune-related adverse events occurred in 33.3% of patients. High tumor mutational burden was observed in three patients with UV-AS, two of whom showed a response. High intratumoral CD3<sup>+</sup> (<i>P</i> = 0.019), CD4 (<i>P</i> = 0.046), CD8<sup>+</sup> (<i>P</i> = 0.026), and FoxP3<sup>+</sup> (<i>P</i> = 0.026) T-cell densities; low platelet-to-lymphocyte ratio (<i>P</i> = 0.026); and <i>Colidextribacter</i> abundance were associated with response.</p>Conclusions:<p>Cemiplimab shows promising effectivity in sAS and warrants further investigation. Promising predictive blood and tissue biomarkers were identified, indicating potential for improved patient selection.</p></div>