A phase I study of TRK-950, an Anti-CAPRIN-1 antibody, as monotherapy and in combination with nivolumab in Japanese patients with advanced solid tumors.

CAPRIN-1 is a cytoplasmic phosphoprotein strongly expressed on the membrane surface of cancer cells in most solid tumors but not on normal cells. TRK-950 is a first-in-class humanized antibody that targets CAPRIN-1 and demonstrates antitumor effects via immune cell engagement. This phase I study assessed the tolerability and safety of TRK-950 in Japanese patients, both as monotherapy and in combination with nivolumab, and evaluated pharmacokinetic and exploratory efficacy. Part 1 involved TRK-950 monotherapy at 5 or 10 mg/kg weekly for patients with advanced solid tumors; Part 2 included combination therapy with TRK-950 (10 mg/kg weekly or 20 mg/kg biweekly) plus nivolumab (240 mg biweekly). The primary endpoints were safety and tolerability; the secondary endpoints were pharmacokinetics, immunogenicity, and exploratory antitumor activity. Thirteen patients were enrolled. No dose-limiting toxicity occurred. Adverse events (AEs) of any grade with a frequency ≥ 20% were, in Part 1, alanine aminotransferase increased, constipation, and nausea and, in Part 2, pyrexia. The incidence of AEs did not appear to be dose dependent. In Part 1, 1 patient with melanoma achieved a partial response, and the response was sustained for an extended period. In Part 2, no responses were observed. TRK-950, as monotherapy or combined with nivolumab, was safe and well tolerated in Japanese patients with observed antitumor activity. TRK-950 is currently being evaluated in ongoing clinical studies: phase II study in patients with melanoma (NCT05423262) and phase II study in patients with gastric cancer (NCT06038578).Trial registration ClinicalTrials.gov, NCT05423262.