Phase I trial of the anti-CAPRIN1 antibody TRK-950 alone or with nivolumab in Japanese patients with advanced solid tumors.

2525 Background: CAPRIN-1 is expressed on the tumor-cell membrane across many solid cancers but not on normal cells. TRK-950 is a first-in-class humanized IgG1 that mediates antibody-dependent cellular phagocytosis and cytotoxicity. A series of pre-clinical studies demonstrates its potency and safety. In the phase I study of TRK-950 monotherapy (NCT02990481) in US and France, it appears safe and well tolerated. No DLT was observed and MTD was not reached at doses of 3-30mg/kg IV weekly. Here, we evaluated safety/tolerability, pharmacokinetics (PK), and preliminary antitumor activity in Japanese patients with advanced solid tumors. Methods: Open-label, single-center, dose-escalation study in Japan (NCT05423262). Part 1 evaluated TRK-950 at 5 or 10 mg/kg IV weekly in patients with locally advanced or metastatic solid tumors. Part 2 evaluated TRK-950 at 10 mg/kg weekly or 20 mg/kg every 2 weeks in combination with nivolumab 240 mg every 2 weeks in patients with locally advanced or metastatic solid tumors who were eligible for standard nivolumab monotherapy. Primary endpoints were safety/tolerability (DLT; Treatment-related AEs per CTCAE v5.0). Secondary endpoints included PK, immunogenicity, and antitumor activity by RECIST v1.1. Results: Thirteen patients were treated (Part 1 n=7; Part 2 n=6). No DLTs occurred and the MTD was not reached; both monotherapy and combination regimens were well tolerated. TRK-950 PK was consistent with IgG1; exposures were comparable between 10 mg/kg weekly and 20 mg/kg every 2 weeks, with no meaningful PK interaction with nivolumab. In Part 1, a partial response was achieved in a patient with melanoma achieved a partial response, and the response was sustained for an extended period. In Part 2, no response were observed. Conclusions: TRK-950, as monotherapy and with nivolumab, was safe and tolerable in Japanese patients with advanced solid tumors. Durable antitumor activity with monotherapy supports continued development. Both the 10 mg/kg weekly and the more convenient 20 mg/kg biweekly dosing regimens of TRK-950 in combination with nivolumab were safely administered, supporting the potential for further development of this combination. Clinical trial information: NCT0542326 .