Phase I first-in-human Study of TRK-950, an IgG1 Antibody Specific to CAPRIN-1, in Patients with Advanced Solid Tumors.

Purpose: TRK-950 is a first-in-class humanized antibody targeting CAPRIN-1, which is strongly expressed on the cell membrane surface in or on most solid tumors but not in or on normal tissues. This first-in-human study investigated the safety profile, pharmacokinetics and preliminary antitumor activity.

Patients and methods: Patients with treatment refractory, locally advanced or metastatic solid tumors were enrolled in dose escalation/expansion study. TRK-950 was administered intravenously weekly for three weeks in a 28 day cycle, with doses ranging from 3-30 mg/kg. Dose expansion included 10 mg/kg weekly and 30 mg/kg biweekly for colorectal cancer, and 10 mg/kg weekly for cholangiocarcinoma. The primary objective of this study was to determine its safety, tolerability, and MTD. The secondary objectives were pharmacokinetics, preliminary antitumor activity, and identification of potential biomarkers.

Results: 36 patients received at least one dose of TRK-950. In the Dose Escalation Cohort, the maximum tolerated dose was not reached, and no dose-limiting toxicities were observed up to 30 mg/kg. Common adverse events included abdominal pain, fatigue, constipation, back pain, nausea, and decreased appetite. TRK-950 exhibited a PK profile similar to that of other IgG1 therapeutic antibodies, with linear PK parameters over the 3-30 mg/kg dose range. The best response was stable disease. Notably, one cholangiocarcinoma patient showed signs of cavitation after approximately eight months, suggesting potential antitumor activity.

Conclusions: TRK-950 is safe and well tolerated, has a favorable PK profile, and should be further investigated as a monotherapy and in combination with standard treatment for various types of solid tumors.