Phase II study of YS110, a recombinant humanized anti-CD26 monoclonal antibody, in Japanese patients with advanced malignant pleural mesothelioma

Abstract Introduction YS110, a humanized monoclonal antibody with high affinity to CD26, showed promising antitumor activity and was generally well tolerated in the phase I part of a phase I/II Japanese trial in patients with malignant pleural mesothelioma (MPM). Here we report results of the phase II part of the study. Methods Patients were aged ≥20 years, had histologically confirmed MPM, were refractory to or intolerant of existing antineoplastic agents, and were not candidates for standard therapy. YS110 6 mg/kg, determined in the phase I dose-finding part, was given in 6-weekly cycles (5 x once-weekly infusions, followed by a 1-week rest). Results The study included 31 patients (median age 68 years, 90.3% men); 64.5% had stage IV MPM, 90.3% had ≥20% CD26 expression in tumor tissue, and 38.7% (12 patients) had previously received nivolumab. The 6-month disease control rate (DCR) was 3.2%. Best overall response was partial response in one patient and stable disease in 14 patients. Median progression-free survival (PFS) was 2.8 months (both in patients who had and had not previously received nivolumab, groups A and B, respectively). Respective PFS rates at 6 months were 9.1% and 31.6% in groups A and B. Median overall survival (OS) was 9.7 months. Thirty patients (96.8%) had at least one adverse event (AE). Common treatment-related AEs were infusion-related reaction (16.1%), hiccups (9.7%), and interstitial lung disease (9.7%). There were no treatment-related deaths. Conclusions The 6-month DCR did not exceed the pre-defined threshold, but YS110 showed modest efficacy in response rate as a salvage therapy in difficult-to-treat MPM patients. YS110 was generally well tolerated.