BNT211 comprises two drug products, a chimeric antigen receptor (CAR)-T cell product candidate that targets the tumor specific antigen claudin 6 (CLDN6) and a CAR_T cell-Amplifying RNA Vaccine (CARVac). In mice, CARVac mediates expansion of adoptively transferred CAR-T cells, improving their persistence and functionality.

This FIH, open label, multi-center trial involves a bifurcated 3+3 design with CLDN6 CAR-T cell dose escalations for both monotherapy (Part 1) and combination with CARVac (Part 2) following lymphodepletion. Patients with CLDN6-positive relapsed or refractory solid tumors without further standard treatment options and ECOG 0-1 are eligible for recruitment.

As of 18th Nov 2021, 15 patients had been treated. Part 1, dose levels (DLs) 1 and 2 and Part 2, DL1 had been completed, while Part 2, DL2 was ongoing. Few adverse events related to the drug product and a single DLT mainly linked to the lymphodepletion regimen have been reported. Manageable cytokine release syndrome (grade 1-2) without any signs of neurotoxicity has been observed in 7 patients. Transient, moderate elevations of IL-6 serum levels occurred in remaining patients. Notably, CARVac resulted in flu-like symptoms resolving within 24 h. Analysis of CAR-T cell frequency in peripheral blood revealed robust engraftment in all patients. Preliminary efficacy data for 10 evaluable patients 6 weeks post-infusion showed 4 partial responses, 1 progressive disease and 5 stable disease.

Taken together, CLDN6 CAR-T cells ± CARVac show a moderate safety profile at doses tested and encouraging signs of clinical activity. BNT211-01 (NCT04503278) is funded by BioNTech Cell & Gene Therapies GmbH.