Multinational phase 1 study of trispecific CB307 in patients with PSMA-positive solid tumors

CB307 is a trispecific antibody fragment against PSMA, CD137, and human serum albumin. It is designed to mitigate hepatoxicity by activating T cells only in PSMA-positive tumors and to increase drug half-life through albumin binding. A multinational phase 1 trial evaluated CB307 as monotherapy and in combination with pembrolizumab in heavily pretreated patients with PSMA-positive solid tumors. CB307 was given once every 7 days. Two dose-limiting toxicities (grade 3 transient transaminitis) were observed. A total of three grade 3 transaminitis events (one in the monotherapy cohort and two in the combination cohort) were observed, and none involved bilirubin elevation. Durable RECIST responses were observed in two mCRPC patients enrolled in the 800 mg CB307 monotherapy cohort (ORR 11.1%) and one mCRPC patient in the combination cohort (ORR 7.1%). A disease control rate of 50% was observed in patients enrolled in the 800 mg CB307 monotherapy cohort and 42.9% in the combination cohort. In a post hoc analysis, the response was numerically better in patients who had not received chemotherapy in the 6 months prior to starting CB307 (ORR 20% and DCR 60% versus ORR 0% and DCR 37.5%). The authors conclude that CB307 was well tolerated as monotherapy and in combination with pembrolizumab, and tumor responses were observed in patients with mCRPC.