Phase 2 Study of YS110, a Recombinant Humanized Anti-CD26 Monoclonal Antibody, in Japanese Patients With Advanced Malignant Pleural Mesothelioma.

INTRODUCTION: YS110, a humanized monoclonal antibody with a high affinity to CD26, exhibited promising antitumor activity and was generally well-tolerated in the phase 1 part of a phase 1 and 2 Japanese trial in patients with malignant pleural mesothelioma (MPM). Here we report the results of the phase 2 part of the study. METHODS: The patients included were aged 20 years and older, 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 1 dose-determination part, was given in 6-weekly cycles (5 × once-weekly infusions, followed by a 1-wk rest). RESULTS: The study included 31 patients (median age = 68 y, 90.3% men); 64.5% had stage IV MPM, 90.3% had greater than or equal to 20% CD26 expression in tumor tissue, and 38.7% (12 patients) had previously received nivolumab. The 6-month disease control rate was 3.2%. The best overall response was partial response in one patient and stable disease in 14 patients. The median progression-free survival was 2.8 months (both in patients who had and had not previously received nivolumab-groups A and B, respectively). Respective progression-free survival rates at 6 months were 9.1% and 31.6% in groups A and B. The median overall survival was 9.7 months. A total of 30 patients (96.8%) had at least one adverse event. Common treatment-related adverse events 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 disease control rate did not exceed the predefined threshold, but YS110 revealed modest efficacy in response rate as salvage therapy in difficult-to-treat patients with MPM. YS110 was generally well tolerated.

Synthesis and Properties of a Cyclohexa-2,7-anthrylene Ethynylene Derivative.

The synthesis of a cyclohexa-2,7-(4,5-diaryl)anthrylene ethynylene (1) was achieved for the first time by using 1,8-diaryl-3,6-diborylanthracene and 1,8-diaryl-3,6-diiodoanthracene as key synthetic intermediates. Macrocycle 1 possesses a planar conformation of approximately D6h symmetry, because of the triple-bond linker between the anthracene units at the 2,7-positions. It was confirmed that macrocycle 1, bearing bulky substituents at the outer peripheral positions, behaves as a monomeric form in solution without π-stacking self-association. Macrocycle 1 has an inner-cavity size that allows specific inclusion of [9]cycloparaphenylene ([9]CPP), but not [8]CPP or [10]CPP, through an aromatic edge-to-face CH-π interaction.