1734P - Evaluation of nivolumab in cutaneous angiosarcoma management: The ANGIOCHECK study

Background

Taxane-based chemotherapy stands as the frontline therapy for unresectable cutaneous angiosarcoma, yet a standardized approach for non-responsive cases remains elusive.

Methods

To address this gap, we initiated a multicenter, single-arm phase II trial to assess the efficacy and safety of ONO-4538 (Nivolumab), an anti-PD-1 monoclonal antibody. Patients with cutaneous angiosarcoma resistant to taxane-based chemotherapy was enrolled. Nivolumab was administered at a dosage of 480mg every 4 weeks. The primary endpoint was centrally evaluated best overall response rate, with secondary endpoints including response rate evaluated by participating institutions and disease control rate.

Results

Among the 23 enrolled patients, institutional assessment revealed a response rate of 21.7%, with 5 partial responders. Centrally assessed, the response rate stood at 13.0%, with 3 confirmed partial responders, along with an additional patient showing an unconfirmed partial response. Falling short of statistical significance, with a requirement of at least 4 responders out of 23 cases, the study did not meet the predetermined level of significance. In terms of safety, no new signals emerged. In-Depth genomic analysis via whole exome sequencing in 16 cases identified a high tumor mutational burden (TMB) in 7 cases (44%). Interestingly, among patients with high TMB, 1 achieved a partial response and 3 attained stable disease (response rate: 14.3%, disease control rate: 57.1%), compared to 2 partial responses with no stable disease in 9 patients with lower TMB (response rate: 28.6%, disease control rate: 28.6%).

Conclusions

Despite the failure to meet the predetermined level, Nivolumab exhibited efficacy in a subset of cutaneous angiosarcoma patients refractory to taxane therapy. Presently, only those with high TMB can access anti-PD-1 antibody pembrolizumab in Japan. Notably, our findings indicate a lack of correlation between tumor mutational burden and response within our cohort, suggesting a nuanced relationship that warrants further exploration.

Clinical trial identification

UMIN000043039.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Ono pharmaceutical.

Disclosure

Y. Fujisawa: Financial Interests, Institutional, Funding: Ono pharmaceutical. All other authors have declared no conflicts of interest.