Phase II trial dedicated to non-selected, pretreated cutaneous angiosarcoma: Efficacy of nivolumab (AngioCheck Study)

Background: Angiosarcoma is a rare and aggressive malignancy with limited treatment options. This phase II, multicenter, open-label, single-arm study (AngioCheck) evaluated the efficacy and safety of nivolumab in patients with cutaneous angiosarcoma previously treated with taxane-based chemotherapy. Methods: Eligible patients had histologically confirmed cutaneous angiosarcoma, prior treatment with docetaxel or paclitaxel, and at least one measurable lesion. Patients received nivolumab 480 mg every four weeks. The primary endpoint was the centrally reviewed overall response rate (ORR). Secondary endpoints included investigator-assessed ORR, overall survival (OS), and progression-free survival (PFS). An exploratory biomarker analysis was conducted to assess tumor mutational burden (TMB). Results: Twenty-three patients were enrolled across 11 institutions in Japan. The investigator-assessed ORR was 21.7 % (5 patients with partial response [PR], while the centrally reviewed ORR was 13.0 % (3 PR; 90 % CI: 3.7–30.4), which did not meet the predefined success threshold. The median OS was 259 days (90 % CI: 188.0–387.0), and the median PFS was 59 days (90 % CI: 57–112). TMB analysis was performed in 16 patients: among TMB-high patients (n = 7), there were 0 PR and 3 stable disease (SD); among non-TMB-high patients (n = 9), 2 PR and 1 SD were observed. Although the TMB-high group had a numerically higher disease control rate (PR + SD; 42.9 % vs. 33.3 %), no significant association between TMB status and treatment response was found. Conclusions: Nivolumab monotherapy did not achieve the predefined response rate in this cohort of pretreated cutaneous angiosarcoma patients. No correlation between TMB-high status and objective response was identified. Further investigations are needed to explore predictive biomarkers and combination strategies to improve therapeutic efficacy.