611O - Updated results from BNT211-01 (NCT04503278), an ongoing, first-in-human, phase I study evaluating safety and efficacy of CLDN6 CAR T cells and a CLDN6-encoding mRNA vaccine in patients with relapsed/refractory CLDN6+ solid tumors

Background

Investigational therapy combining chimeric antigen receptor (CAR) T cells targeting the oncofetal antigen claudin 6 (CLDN6) with a CLDN6-encoding CAR T cell-Amplifying RNA Vaccine (CARVac) showed promising activity in relapsed/refractory (r/r) CLDN6+ tumors (ESMO 2022 LBA38; ESMO 2023 LBA35). Here, we present updated results from ongoing first-in-human BNT211-01 (NCT04503278) study from cohorts receiving automated process manufactured CAR T ± CARVac.

Methods

Patients (pts) had r/r CLDN6+ solid tumors, ECOG performance status 0–1 and no further standard treatment options. Following lymphodepletion (LD), pts received CAR T cells at 5 dose levels (DL0=1×10⁶; DL1=1×10⁷; DL1.5=5×10⁷; DL2=1×10⁸; DL3=2–5×10⁸) ± repeat CLDN6 CARVac dosing (1×50 μg, then 100 μg doses). Primary endpoints are safety and tolerability. Secondary endpoints are efficacy and pharmacokinetics.

Results

As of 08 Jan 2024, 59 pts (median age 48 years; 56% male; median 4 prior treatment lines [range 1–9]) received automated process manufactured CAR T cells alone (n=26) or with CARVac (n=33). Treatment-related adverse events (TRAE), including related to LD, occurred in 52 pts (88%); Grade (G) 3+ TRAE in 38 pts (64%); serious related AE in 23 pts (39%). Dose-limiting toxicities, AE of special interest, treatment discontinuations and deaths are shown in the table. Table: 611O

^aGraded per ASTCT; ^bExcludes 1 fatal AE related to LD; CRS, cytokine release syndrome; DLT, dose-limiting toxicity; IEC-HS, immune effector cell-associated HLH-like syndrome; HLH, hemophagocytic lymphohistiocytosis.

CAR T cell persistence beyond 90 days was observed in 1/5 pts who received DL2 and in 5/7 pts who received DL2 + CARVac. Overall, objective response rate (ORR) was 38% (20/52); disease control rate (DCR) was 69% (36/52). Among pts who received DL2 or DL3 after 100% LD ± CARVac, ORR was 55% (16/29 pts), DCR was 86% (25/29 pts). Follow up is ongoing; updated results will be presented.

Conclusions

CLDN6 CAR T cells ± CARVac showed treatment-related safety signals and promising antitumor activity in pts with r/r CLDN6+ solid tumors.

Clinical trial identification

NCT04503278.

Editorial acknowledgement

Medical writing support was provided by Olga Ucar of BioNTech UK Ltd.

Legal entity responsible for the study

BioNTech Cell & Gene Therapies GmbH.

Funding

BioNTech Cell & Gene Therapies GmbH.

Disclosure

J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squipp, Achilles Therapeutics, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Iovance Biotherapeutics, AstraZeneca; 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, Advisory Board: Third Rock Venture, CureVac, Imcyse; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio, Sastra Cell Therapy; Non-Financial Interests, Member: ASCO, AACR, SITC; Other, Editor-in-Chief IOTECH: ESMO; Other, Editorial Board ESMO Open: ESMO; Other, Editorial Board: Kidney Cancer. A. Mackensen: Financial Interests, Personal, Advisory Board: Miltenyi Biomedicine, KITE/Gilead, Novartis, BMS/Celgene, BioNTech. C. Schultze-Florey: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Pierre Fabre, Gilead; Financial Interests, Personal, Other, Travel support: Pierre Fabre, Gilead. W. Alsdorf: Financial Interests, Personal, Other, Travel and accommodation costs: BioNTech, Immatics, Janssen; Financial Interests, Personal, Other, Honoraria: GSK, AstraZeneca, Astellas; Financial Interests, Institutional, Research Funding: BioNTech, Affimed; Financial Interests, Personal, Other, Medical writing support: BioNTech, Janssen. E. Wagner-Drouet: Financial Interests, Personal, Advisory Board: Takeda, MSD, Kite/Gilead, Novartis, Pfizer, Janssen; Financial Interests, Personal, Other, Travel grant: Medac, Kite/Gilead, Cellgene/BMS; Financial Interests, Personal, Invited Speaker: Kite/Gilead, Takeda. D. Heudobler: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Bristol Myers Squibb, Janssen-Cilag, MSD; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, MSD, Roche, AbbVie; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Sanofi, AbbVie, Bristol Myers Squibb, Janssen-Cilag; Financial Interests, Institutional, Funding: Janssen-Cilag, Bristol Myers Squibb. 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. A. Busse: Financial Interests, Personal, Invited Speaker: Novartis, Glidead, MSD, AStraZeneca; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Institutional, Research Grant, Translational research of the Ribecca Trial: Novartis. S. Mielke: Financial Interests, Institutional, Invited Speaker, Travel support, Expert panel (via my institution): KITE/Gilead; Financial Interests, Institutional, Invited Speaker, Speaker's bureau (via my institution): Celgene/BMS; Financial Interests, Institutional, Invited Speaker, Speaker’s bureau (via my institution): Novartis, Janssen, Pfizer; Financial Interests, Institutional, Other, Miltenyi: Data safety monitoring board (via my institution): Miltenyi; Financial Interests, Institutional, Other, Immunicum/Mendes: Data safety monitoring board (via my institution): Immunicum/Mendes; Other, SWECARNET: Founder/Leadership (via my institution): SWECARNET; Other, Founder (spouse): ScientifyResearch. S. Bins: Financial Interests, Institutional, Research Grant: Nordic Pharma. 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, Oncology Drug Consult CRO, Lindis Biotech, BioNTech, Heaxal; Financial Interests, Personal, Advisory Board, Boards attended and lectures given: Sanofi Aventis; Financial Interests, Personal, Advisory Board, advisory board and speaker: AstraZeneca; Financial Interests, Personal, Invited Speaker, organisation for medical education: Med Update; Financial Interests, Institutional, Local PI, our department is involved in several clinical trials sponsored by industry and cooperative groups where we hold participants roles and local PI roles and PI roles: more than 95 clinical trials; Non-Financial Interests, Advisory Role: DGHO; Non-Financial Interests, Leadership Role: Hamburg Cancer Society, National Network of German Cancer Centers (DKH); Non-Financial Interests, Member of Board of Directors: Northern German Society of Internal Medicine; Non-Financial Interests, Advisory Role, Board of DGHO Advisors: DGHO; Non-Financial Interests, Advisory Role, Board of Directors Oncology Center Certification Committee: German Cancer Society. S. Klobuch: Financial Interests, Institutional, Advisory Board: Regeneron; Financial Interests, Institutional, Local PI: Neogene. N. Kutsch: Financial Interests, Personal, Invited Speaker: AstraZeneca, Roche; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Institutional, Funding: Gilead, AstraZeneca; Non-Financial Interests, Member: EHA; Other, Travel Grants: AbbVie, AstraZeneca, Celgene, Janssen, Gilead. F. Müller: Financial Interests, Personal, Advisory Board: ArgoBio, AstraZeneca, BMS, CRISPR Therapeutics, EcoRI, Janssen, Kite/Gilead, Miltenyi, Novartis; Financial Interests, Personal, Invited Speaker: Incyte, Sobi, Takeda; Financial Interests, Institutional, Research Grant: AstraZeneca, Kite/Gilead. A. Desuki: Financial Interests, Personal, Advisory Board: BMS, MSD, Roche; Financial Interests, Personal, Invited Speaker: Janssen-Cilag. W. Zhong, L. Preussner: Financial Interests, Personal, Full or part-time Employment: BioNTech; Financial Interests, Personal, Stocks/Shares: BioNTech. Ö. Türeci: Financial Interests, Personal, Full or part-time Employment: BioNTech; Financial Interests, Personal, Stocks/Shares: BioNTech; Financial Interests, Personal, Leadership Role: BioNTech; Financial Interests, Personal, Funding: BioNTech, HI-TRON Mainz; Financial Interests, Personal, Licencing Fees or royalty for IP: BioNTech, HI-TRON Mainz; Financial Interests, Personal, Other, Travel and accommodation expenses: BioNTech; Non-Financial Interests, Personal, Advisory Role, Member of the scientific management board: HI-TRON; Non-Financial Interests, Personal, Advisory Role, President of the association for cancer immunotherapy: CIMT. U. Sahin: Financial Interests, Personal, Full or part-time Employment: BioNTech; Financial Interests, Personal, Stocks/Shares: BioNTech; Financial Interests, Personal, Leadership Role: BioNTech; Financial Interests, Personal, Funding: BioNTech; Financial Interests, Personal, Licencing Fees or royalty for IP: BioNTech, Tron; Financial Interests, Personal, Other, Travel and accommodation expenses: BioNTech; Non-Financial Interests, Personal, Advisory Role, Co-founder and scientific advisor: TRON; Non-Financial Interests, Personal, Advisory Role, Member of the scientific management board: HI-TRON. All other authors have declared no conflicts of interest.