BioNtech SE has reported preliminary Phase I/II results with BNT211-01 (NEO-PTC-01) and CarVAC at ESMO conference in Madrid

Testing different dose levels of its adoptive cell therapy BNT.221-01, a combination of Claudin 6 (CLDN6)-targeted Car-T cells (derived from NEO-PTC-01, initially developed by tody’s BioNTech subsidiary Neon Therapeutics) and the mRNA-based Car-T  booster CarVac (CAR-T cell amplifying RNA vaccine), BioNtech reported acceptable safety and tolerability data and first hints to efficacy in solid tumours at the ESMO conference in Madrid.

CLDN6 is only produced by healthy cells in the fetal phase, but is no longer needed later. The genetic chaos that occurs in the context of cancer leads to CLDN6 reappearing on the cell surface in some tumours, where it can become a target for CAR-T cells as a neoantigen.

In the dose escalation trial (NCT04503278) CLD6-positive patients were treated with CAR T cells manufactured by an automated process and increased CARVac dosage. Following lymphodepletion, CAR T cells were dosed at four dose levels (DLs, 1×10⁶ up to 2-5×10⁸ CAR-T cells) plus ± repeat CLDN6 CARVac dosing (1×50 μg, then 100 μg doses). Primary endpoints are safety and tolerability.

As of 25 July 2023, 38 patients, most of which with with ovarian cancer (14) and with germ cell tumours (11) were treated. Treatment emergent adverse events (TEAEs) obove grade 3 were observed in 23 patients (61%), including 20 (53%) with TEAEs related to CAR-T cells. From 21 patients treated with the combination, nine (43%) had TEAEs above grade three related to both drugs, and two (10%) to CARVac. Related TESAEs were observed in eight patients (21%). Dose limirting toxiciities (DLTs) occurred in two patients from different cohorts, grade 4 cytokine release syndrome (CRS) at 5×10⁸ CAR-T cells and grade 4 pancytopenia at 1×10⁸, hence an maxumum tolerated dose (MTD) could not be determined. One death was assessed as treatment-related after the data cut-off. However, cytokine-release syndrome, which generally occurs in patients treated with Car-T cell therapy, was predominantly (95%) grade 1 or 2 and observed in 18 (47%) patients.

It is still too early to assess the efficacy. However, 28 efficacy-evaluable patients, 9 patients (32%) showed a partial response and a further nine had stable disease ([SD], so theoretically the unconfirmed overall response rate [ORR] would be 32%, the disease control rate [DCR]: 64%. Of 19 patientsd treateda higher dose of Car-T cells, eight showed partial response and further eight stable disease resulting in an unconfirmed ORR of 42% and a disease control rate of 84%. CAR-T expansion was dose-dependent, with improved persistence by addition of CARVac.

According to BioNTec, the combination of Claudin 6-targeted CAR T cells and CARVac demonstrated encouraging antitumour activity. the company did not quantify how much addition of CARVac improved CAR-T cell persistence. The safety profile observed was in line with previously reported observations. In September, BioNtech intends to present data on up to 42 patients.

The hype made in some media reporting BioNTech’s combo was the first in which Car-Ts showed preliminary efficacy in solid tumours was unfounded because companies such as TCR² previously reported similar data with a TCR-T candidate in advanced clinical stage.