Tucidinostat plus toripalimab in patients with unresectable or metastatic melanoma: An open-label, single-arm phase II study.

e21527 Background: Acral and mucosal melanoma respond poorly to anti–PD-1 monotherapy. Tucidinostat, a benzamide class of histone deacetylase (HDAC) inhibitor, potentially augments immunotherapy with PD-1 blockade. We therefore conducted a phase II study to investigate the safety and efficacy of tucidinostat plus toripalimab in unresectable or metastatic melanoma. Methods: This was a single center, single arm phase II clinical trial. Patients with pathologically confirmed locally advanced unresectable or metastatic melanoma were enrolled and received 30 mg tucidinostat orally twice a week and 240 mg toripalimab every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint was the confirmed ORR per RECIST v1.1. Secondary endpoints included progression free survival (PFS), disease control rate (DCR), overall survival (OS), and safety. Results: Between October 2022 and May 2023, a total of 21 patients(pts) were enrolled. All pts were included in the safety analysis set and 18 pts were included in the full analysis set (FAS) for efficacy analysis. In the FAS, the median age was 56.0 years (range: 49 to 60), 6 pts (33.3%) were acral melanoma, 9 (50.0%) mucosal melanoma, 1 (5.6%) cutaneous melanoma and 2 (11.1%) unknown primary melanoma. 15 pts were treated as first-line, and 3 pts were as second-line. By Dec 2023, the median follow-up was 8.8 mo (95% CI:7.6-10.4) , Confirmed ORR was 27.8% (95% CI:9.7-53.5%). The DCR was 61.1% (95% CI:35.7-82.7%). Median progression-free survival was 4.1 months (95%CI: 1.4-NR) ,OS was not reached. Subgroup analysis showed that, in acral and mucosal melanoma pts, the confirmed ORR was 50.0%(95%CI:11.8-88.2%) and 22.2%(95%CI: 2.8-60.0%), respectively. The incidence of treatment-related adverse events (TRAEs) was 90.5% (19/21). The most common ≥3 grade TRAEs were neutrophil reduction (28.6%), white blood cell count reduction (9.5%), alanine aminotransferase increase (9.5%), platelet count reduction (9.5%), aspartate aminotransferase increase (9.5%), and γ-glutamyl transferase increase (9.5%). No treatment-related deaths occurred. Conclusions: The combination of tucidinostat and toripalimab showed acceptable safety and encouraging efficacy in patients with unresectable or metastatic melanoma. Further research is warranted. Clinical trial information: NCT05478473 .