Abstract
<div>AbstractPurpose:<p>This is a phase Ib trial of TAS-116, an oral HSP90 inhibitor, plus nivolumab for colorectal cancer and other solid tumors.</p>Patients and Methods:<p>Enrolled patients received TAS-116 plus nivolumab in a dose-finding part to estimate the recommended dose. Additional patients were enrolled in a dose-expansion part. TAS-116 monotherapy (orally once daily, 80–160 mg) was administered for 2 weeks followed by the combination with nivolumab (intravenously every 2 weeks, 3 mg/kg). The primary endpoint was dose-limiting toxicities (DLT). We also conducted biomarker research using paired samples from repeated blood collections and tumor biopsies.</p>Results:<p>A total of 44 patients with colorectal cancer (<i>n</i> = 29), gastric cancer (<i>n</i> = 8), sarcoma (<i>n</i> = 5), non–small cell lung cancer (<i>n</i> = 1), and melanoma (<i>n</i> = 1) were enrolled. Eleven patients had previously received immune-checkpoint inhibitors. No DLTs were observed at all dose levels, and TAS-116 160 mg was determined as recommended dose. The common grade 3 or worse treatment-related adverse events included liver transaminase increased (7%), creatinine increased (5%), and platelet count decreased (5%). Objective tumor response was observed in 6 patients, including 4 microsatellite stable (MSS) colorectal cancers, 1 microsatellite instability-high colorectal cancer, and 1 leiomyosarcoma, resulting in an objective response rate of 16% in MSS colorectal cancer without prior immune-checkpoint inhibitors. Biomarker analysis showed that TAS-116 inhibited the activity of regulatory T cells in peripheral blood mononuclear cells and tumor-infiltrating lymphocytes.</p>Conclusions:<p>TAS-116 160 mg plus nivolumab had manageable safety profiles and antitumor activity, especially for MSS colorectal cancer patients.</p></div>
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