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). Preclinical studies demonstrated that CARVac mediates in vivo expansion of CAR-T cells, resulting in their improved persistence and functionality. Therefore, BNT211 aims to improve CAR-T therapy for solid tumors.
This first-in-human, open label, multi-center trial involves a bifurcated 3+3 design with separate CLDN6 CAR-T cell dose escalations (single flat-dose) for monotherapy (Part 1) and the combination with CARVac (Part 2) based on 3 dose levels (DLs). In Part 2, CARVac is applied every 3 weeks starting at Day 4 post transplantation including a one-step intra-patient dose escalation. Patients with CLDN6-positive relapsed or refractory solid tumors without further standard treatment options and ECOG 0 or 1 are eligible for recruitment.
As of 16th September 2021, 9 patients had been treated within three cohorts. DL1 of Parts 1 and 2 had been completed, while DL2 of Part 1 was ongoing. No dose-limiting toxicities and only a few adverse events related to the drug product and mainly linked to the lymphodepletion regimen have been reported. Pronounced cytopenia occurred in patients with testicular cancers who had recently received high dose chemotherapy and autologous stem cell transplantation. For these patients a lymphodepletion free cohort was recently opened. Manageable cytokine release syndrome (CRS, grade 1 to 2) without any signs of neurotoxicity has been observed in 1 patient of Part 2 DL1 and all patients of Part 1 DL2. Transient and moderate elevations of IL-6 serum levels occurred in remaining patients. Notably, administration of CARVac resulted in transient flu-like symptoms resolving within 24 h. Analysis of CAR-T cell frequency in peripheral blood revealed robust engraftment in all patients. First preliminary efficacy data shows tumor shrinkage in 3 of 5 evaluable patients.
CLDN6 CAR-T cells ± CARVac show a favorable safety profile at doses tested and encouraging signs of clinical activity. Updated data from open cohorts will be presented.
NCT04503278.
J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: BMS, Ipsen, Merck Serono, Molecular Partners, MSD, Novartis, Pfizer, Roche/Genentech, Sanofi, Third Rock Ventures; Financial Interests, Institutional, Advisory Board: Achilles Tx, BioNTech US, Gadeta, Immunocore, Instil Bio, PokeAcel, T-Knife, Neogene Therapeutics; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Non-Financial Interests, Personal and Institutional, Member, Editor-in-Chief: ESMO IOTECH; Non-Financial Interests, Institutional, Funding, Grant support: Amgen, Asher Bio, BioNTech US, BMS, MSD, Novartis, Neogene Therapeutics. A. Mackensen: Financial Interests, Personal, Advisory Board: Miltenyi Biomedicine, Gilead/Kite, Novartis, BMS/Celgene, Ixaka; Financial Interests, Personal, Invited Speaker: Gilead/Kite, Novartis, BMS/Celgene. C. Koenecke: Financial Interests, Personal, Advisory Board: Janssen, Novartis, BMS/Celgene, Amgen, Sanofi, EUSAPharm, Gilead/Kite, Roche, GSK, Medigene. A. Desuki: Financial Interests, Personal, Advisory Board: Janssen, BMS, MSD, Eisei, Bayer; Financial Interests, Personal, Invited Speaker: BMS, Pfizer, Janssen. E. Wagner-Drouet: Financial Interests, Personal, Advisory Board: Novartis, Gilead/Kite, MSD. D. Heudobler: Financial Interests, Personal, Advisory Board: BMS, MSD, Janssen, Roche, Pfizer, Boehringer; Financial Interests, Institutional, Funding: BMS; Financial Interests, Personal, Speaker’s Bureau: BMS, Novartis. P. Borchmann: Other, Personal, Advisory Board: Roche, Amgen; Other, Personal, Invited Speaker: BMS, Celgene, AbbVie; Other, Personal and Institutional, Sponsor/Funding: Takeda Oncology, Novartis, MSD; Other, Personal and Institutional, Principal Investigator: Miltenyi Biotech; Other, Personal and Institutional, Advisory Board: Gilead. E. Wiegert: Financial Interests, Personal, Other, Consultant: BioNTech, Casi, Exicure, InflaRx, iTeos therapeutics, Molecular templates, Pieris, Roche, RS Oncology, Sapience, Vyriad Inc. C. Schulz: Financial Interests, Personal, Full or part-time Employment: BioNTech SE. B. Rengstl: Financial Interests, Personal, Full or part-time Employment: BioNTech SE; Financial Interests, Personal, Royalties, Holds patents: BioNTech SE. L. Preußner: Financial Interests, Personal, Full or part-time Employment: BioNTech SE. Ö. Türeci: Financial Interests, Personal and Institutional, Member of the Board of Directors, CMO: BioNTech SE; Financial Interests, Personal and Institutional, Ownership Interest, Co-founder: BioNTech SE; Financial Interests, Personal, Stocks/Shares, Co-founder: BioNTech SE; Financial Interests, Personal, Royalties, Holds patents: BioNTech SE; Other, Personal and Institutional, Leadership Role, President: CIMT. U. Sahin: Financial Interests, Personal and Institutional, Member of the Board of Directors, CEO: BioNTech SE; Financial Interests, Personal and Institutional, Ownership Interest, Co-founder: BioNTech SE; Financial Interests, Personal, Stocks/Shares, Co-founder: BioNTech SE; Financial Interests, Personal, Royalties, Holds patents: BioNTech SE; Financial Interests, Institutional, Funding, Grant support from BMBF, DFG, EC: TRON; Financial Interests, Personal and Institutional, Leadership Role, Scientific advisor: TRON; Financial Interests, Personal, Royalties, Holds patents: TRON. All other authors have declared no conflicts of interest.