On October 23, 2023 BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") reported follow-up data from its ongoing first-in-human Phase 1/2 trial (NCT04503278; 2019-004323-20) evaluating the safety and efficacy of the Company’s Claudin-6 (CLDN6)-directed CAR-T cell therapy candidate BNT211 in patients with CLDN6-positive refractory/relapsed solid tumors (Press release, BioNTech, OCT 23, 2023, View Source [SID1234636239]). The data show encouraging signs of clinical activity and an increased persistence of cancer-specific CAR-T cells when combined with CARVac. At the ESMO (Free ESMO Whitepaper) Congress 2023 in Madrid, Prof. John Haanen, M.D., Ph.D., Netherlands Cancer Institute (NKI), Amsterdam, Netherlands presented the data in an oral late-breaking data session which confirms the positive interim data presented at this year’s American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago, USA.

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"Our goal is to unlock the potential of CAR-T for solid tumors and to help improve the outcomes for a broad range of hard-to-treat tumors," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "BNT211 aims to address two of the key limitations of CAR-T cell approaches in solid tumors, namely the lack of suitable cancer-specific cell surface targets and the limited persistence of CAR-T cells. To address this challenge, we have designed a CLDN6-specific autologous CAR-T cell therapy that we combine with our mRNA-based vaccine CARVac."

The data update included 44 patients who received CLDN6 CAR-T cells at four dose levels alone or in combination with CARVac. Patients with germ cell tumors (n=16), ovarian cancer (n=17) and other solid tumor types (n=11) were treated. In course of the dose escalation, a dose-dependent increase in adverse events was observed, with cytokine release syndromes occurring in 23 of 44 safety evaluable patients. In most cases, these were of grade 1 and 2, with one patient with a grade 3 and one with a grade 4 event. Neurotoxicity was mild and self-limiting in two patients. Of the total 44 patients, 38 were efficacy evaluable. The overall response rate ("ORR") for these 38 patients was 45% and the disease control rate ("DCR") 74%. Further, 27 patients were treated with CLDN6 CAR-T cells at dose level 2 (1×108 CAR-T cells) with or without CARVac. At this dose level, 13 patients showed partial responses resulting in an ORR of 59% and a DCR of 95%. Additionally, in the same cohort, patients who received CARVac showed a prolonged persistence of CAR-T cells.

These results further underline the potential of BioNTech’s BNT211 program. One objective of the ongoing Phase 1/2 trial is to determine the recommended dose for the initiation of a potential pivotal Phase 2 trial in patients with germ cell tumors which is expected to be initiated in 2024.

About BNT211
To harness the power of cell therapies for solid cancers, BioNTech has combined their CAR-T and FixVac platform technologies to develop a tumor-specific CAR-T cell therapy which is enhanced by a CAR-T Cell Amplifying RNA Vaccine (CARVac) that is based on BioNTech’s mRNA-lipoplex technology and encodes for the CAR-T target antigen. The mRNA vaccine is designed to boost CAR-T persistence and functionality. BNT211 is a CAR-T cell therapy directed against the novel oncofetal antigen Claudin-6 (CLDN6), a target expressed on multiple solid tumors such as ovarian cancer, sarcoma, testicular cancer, endometrial cancer and gastric cancer. The program is currently being evaluated in a first-in-human Phase 1/2 trial as a monotherapy and in combination with a CLDN6-encoding CARVac in patients with CLDN6-positive relapsed or refractory advanced solid tumors.