Multinational phase 1 trial of CLDN6-specific CAR-T cells plus amplifying RNA vaccine in relapsed or refractory solid tumors

The oncofetal antigen claudin 6 (CLDN6) is specifically expressed in many solid tumors, and could be a promising treatment target. The multinational phase 1-2 BNT211-01 trial evaluated CAR-T cells targeting CLDN6 with or without a CAR-T cell-amplifying RNA vaccine (CARVac) in relapsed or refractory CLDN6-positive solid tumors. The toxicity was manageable (CRS in 46%, grade 3 in 5%; ICANS in 5%, only grade 1). CAR-T cell engraftment was robust, and the addition of CARVac was well tolerated. The unconfirmed ORR was 33% (including one complete response) and the DCR was 67%.