LBA35 - BNT211-01: Interim results from a repeat dose escalation study of CLDN6 CAR-T cells manufactured with an automated process ± a CLDN6-encoding CAR-T cell-amplifying RNA Vaccine (CARVac)

Background

Chimeric antigen receptor (CAR) T cells targeting CLDN6 ± CARVac showed promising activity against relapsed/refractory (r/r) CLDN6+ tumors (ESMO 2022 LBA38). We present data from a repeat 3+3 dose escalation trial with CAR T cells manufactured by an automated process and increased CARVac dosage.

Methods

BNT211-01 is recruiting patients (pts) with CLDN6-positive r/r solid tumours and no further treatment options. Following lymphodepletion, CAR T cells are flat dosed at 4 dose levels (DLs, 1×10⁶ up to 2-5×10⁸ CAR-T cells) ± repeat CLDN6 CARVac dosing (1×50 μg, then 100 μg doses). Primary endpoints are safety and tolerability. Additional endpoints are efficacy and pharmacokinetics.

Results

As of 24.07.2023, 38 pts primarily with ovarian cancer (n=14) and germ cell tumors (n=11) have been treated. Treatment related TEAEs ≥G3 were observed in 23 (61%) pts, including 20 (53%) pts with TEAEs related to CAR T cells. From 21 pts treated with the combination, 9 (43%) pts had TEAEs ≥G3 related to both IMPs, and 2 (10%) to CARVac. Related TESAEs have been observed in 8 pts (21%). DLTs occurred in 2 pts from different cohorts, G4 CRS at 5×10⁸ CAR-T cells and G4 pancytopenia at 1×10⁸, hence an MTD could not be determined. One death was assessed as treatment-related after the data cut-off. CRS was predominantly (95%) G1-2 and observed in 18 (47%) pts. 2 cases each of G1 ICANS and G1 hemophagocytic lymphohistiocytosis were reported (both 5%). Of 28 efficacy-evaluable patients, 9 pts (32%) had partial responses (PRs) and a further 9 had stable disease ([SD], unconfirmed overall response rate [ORR]: 32%, disease control rate [DCR]: 64%). Of 19 pts treated with ≥ 1x10⁸ CAR T cells, 8 PRs and 8 SDs resulted in an ORR of 42% and a DCR of 84%. CAR-T expansion was dose dependent, with improved persistence by addition of CARVac.

Conclusions

CLDN6 CAR T cells ± CARVac demonstrated encouraging antitumor activity. Addition of CARVac improved CAR-T cell persistence. The safety profile in terms of CRS, ICANS and DLTs observed is in line with previously reported observations. We intend to present data on up to 42 pts, with a data cut-off of 10.09.2023.

Clinical trial identification

NCT04503278.

Editorial acknowledgement

Medical writing support was provided by Andrew Finlayson of BioNTech SE.

Legal entity responsible for the study

BioNTech SE.

Funding

BioNTech SE.

Disclosure

A. Mackensen: Financial Interests, Personal, Speaker, Consultant, Advisor: Miltenyi Biomedicine, KITE/Gilead, Novartis, BMS/Celegene; Financial Interests, Personal, Advisory Board: BioNTech; Financial Interests, Advisory Board: Ixaka. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squibb, Achilles Therapeutics, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Third Rock Venture, Iovance Biotherapeutics; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, Immunocore, Gadeta, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics, Scenic; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio; Non-Financial Interests, Member: ASCO, AACR, SITC; Other, Editorial Board ESMO Open: ESMO; Other, Editor-in-Chief IOTECH: ESMO; Other, Editorial Board: Kidney Cancer. W. Alsdorf: Financial Interests, Institutional, Local PI: BioNTech. C. Koenecke: Financial Interests, Personal, Speaker, Consultant, Advisor: GSK, Novartis, Roche, Pierre Fabre, AbbVie, Sanofi-Aventis, Takeda, Kite, BMS, Medigene, Janssen, Amgen; Financial Interests, Institutional, Research Funding: BioNTech. E. Wagner-Drouet: Financial Interests, Personal, Speaker, Consultant, Advisor: Kite Gilead, BMS, Novartis; Financial Interests, Personal and Institutional, Coordinating PI: BioNTech. P. Borchmann: Financial Interests, Personal, Advisory Board: Takeda Oncology, Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Novartis, Miltenyi Biotech, Incyte; Financial Interests, Institutional, Coordinating PI: Takeda Oncology, Roche, Novartis, Merck Sharp & Dohme, Amgen, Miltenyi Biotech. D. Heudobler: Financial Interests, Personal, Research Funding: BMS, Janssen-Cilag; Financial Interests, Institutional, Research Funding: BioNTech. S. Klobuch: Financial Interests, Institutional, Advisory Board: Regeneron; Financial Interests, Institutional, Local PI: Neogene. N. Kutsch: Financial Interests, Institutional, Research Funding: Gilead, AstraZeneca, BioNTech; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: BMS; Financial Interests, Personal, Advisory Board: AstraZeneca. F. Müller: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS; Financial Interests, Institutional, Research Grant: Medimmune. C. Bokemeyer: Financial Interests, Personal, Advisory Board, advisory boards and speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: Roche Pharma, AOK Germany; Financial Interests, Personal, Advisory Board: Bayer Healthcare, AstraZeneca, Oncology Drug Consult CRO, Jansen Cilag, BioNTech; Financial Interests, Personal, Advisory Board, Boards attended and lectures given: Sanofi Aventis; Financial Interests, Personal, Advisory Board, and lectures given: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker, orgaistion for medical education: med update; Financial Interests, Institutional, Local PI, our department is involved in several clincal trials sponsored by industry and cooperative groups where we hold praticipants roles and local PI roles and PI roles: more than 95 clinical trials; Non-Financial Interests, Member of Board of Directors: DGHO, Northern German Society of Internal Medicine; Non-Financial Interests, Leadership Role: Hamburg Cancer Society, National Network of German Cancer Centers (DKH); Non-Financial Interests, Advisory Role, Board of DGHO Advisors: DGHO. A. Desuki: Financial Interests, Institutional, Research Funding: BioNTech. F. Lueke: Financial Interests, Personal, Invited Speaker: Roche, Janssen; Financial Interests, Personal, Advisory Board: Janssen, MSD; Financial Interests, Institutional, Funding: Novartis. T. Ho: Financial Interests, Personal, Full or part-time Employment: BioNTech US; Financial Interests, Personal, Stocks/Shares: BioNTech. K. Vemuri: Financial Interests, Personal, Full or part-time Employment: BioNTech US; Financial Interests, Personal, Stocks/Shares: BioNTech US. L. Preussner: Financial Interests, Personal, Financially compensated role: BioNTech; Financial Interests, Personal, Leadership Role: BioNTech; Financial Interests, Personal, Stocks/Shares: BioNTech. B. Rengstl: Financial Interests, Personal, Financially compensated role: BioNTech; Financial Interests, Personal, Licencing Fees or royalty for IP: BioNTech; Financial Interests, Personal, Project Lead: BioNTech; Financial Interests, Personal, Stocks/Shares: BioNTech. Ö. Türeci: Financial Interests, Personal, Licencing Fees or royalty for IP: BioNTech; Financial Interests, Personal, Leadership Role: BioNTech; Financial Interests, Personal, Member of Board of Directors: BioNTech; Financial Interests, Personal, Ownership Interest, CMO: BioNTech; Financial Interests, Personal, Stocks or ownership: BioNTech. U. Sahin: Financial Interests, Personal, Leadership Role, CEO: BioNTech; Financial Interests, Personal, Licencing Fees or royalty for IP: BioNTech; Financial Interests, Personal, Member of Board of Directors: BioNTech; Financial Interests, Personal, Ownership Interest: BioNTech; Financial Interests, Personal, Stocks or ownership: BioNTech. All other authors have declared no conflicts of interest.