LBA38 - BNT211-01: A phase I trial to evaluate safety and efficacy of CLDN6 CAR T cells and CLDN6-encoding mRNA vaccine-mediated in vivo expansion in patients with CLDN6-positive advanced solid tumours

Background

BNT211 is a potential first-in-class therapeutic approach for claudin 6 (CLDN6)-positive solid tumors with two components: chimeric antigen receptor (CAR) T cells targeting the tumour-specific antigen CLDN6 and a CLDN6-encoding CAR T cell-Amplifying RNA Vaccine (CARVac) designed to expand adoptively transferred CAR T cells and improve their persistence.

Methods

This is a first-in-human trial (NCT04503278) in patients (pts) with CLDN6-positive relapsed/refractory solid tumours, ECOG PS 0/1 and no further standard treatment options. Following lymphodepletion, the bifurcated 3+3 design comprises CLDN6 CAR T cell dose escalations for monotherapy and combined with CLDN6 CARVac, applied repeatedly after CAR T infusion with one intra-pt dose escalation (25→50 μg). Key primary endpoint is safety and tolerability.

Results

As of 15 Jun 2022, 22 pts had been treated, mainly with testicular (13) and ovarian (4) cancers. 7 pts were treated at dose level (DL) 1 (10⁷ CAR T cells/pt; including 1 pt with <10⁷ cells) and 13 pts at DL2 (10⁸ CAR T cells/pt; including 1 pt with a 50% lymphodepletion regimen and 2 pts with no lymphodepletion). 2 pts had dose-limiting toxicities: 1/6 at DL2 monotherapy (pancytopenia), and 1/7 at DL2 + CARVac (hemophagocytic lymphohistiocytosis). Most treatment-emergent adverse events ≥G2 were related to lymphodepletion or asymptomatic transaminase/lipase elevations. Cytokine release syndrome (CRS) was ≤G2, except for 1 pt with no lymphodepletion who had G3 CRS (all resolved). 7/21 evaluable pts (per RECIST v1.1, 6 wks post-infusion) had PR, 8 had SD (6 with target lesion shrinkage) and 6 had PD (including 2 deaths before assessment); as 1 pt was infused with <10⁷ cells they were non-evaluable. 5 pts with testicular cancer responded at 6 wks, with CAR T-cell persistence and further tumour shrinkage; 1 pt was investigator-assessed as CR after 18 wks (negative PET-CT and tumour-marker negative).

Conclusions

CLDN6 CAR T cells ± CLDN6 CARVac had a manageable safety profile in this first-in-human trial, with encouraging signs of clinical activity in pts with limited treatment options.

Clinical trial identification

NCT04503278.

Editorial acknowledgement

Support for third-party writing assistance for this abstract, furnished by John Carron and Islay Steele, of Health Interactions, was provided by BioNTech Cell & Gene Therapies GmbH.

Legal entity responsible for the study

BioNTech Cell & Gene Therapies GmbH.

Funding

BioNTech Cell & Gene Therapies GmbH.

Disclosure

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; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: BMS, Ipsen, Merck Serono, Molecular Partners, MSD, Novartis, Pfizer, Roche/Genentech, Sanofi, Achilles Tx, BioNTech US, Gadeta, Instil Bio, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board: Neogene Therapeutics; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Non-Financial Interests, Institutional, Funding, Grant support: Amgen, Asher Bio, BioNTech US, BMS, MSD, Novartis; Non-Financial Interests, Personal and Institutional, Member, Editor-in-Chief: ESMO IOTECH; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. C. Koenecke: Financial Interests, Personal, Advisory Board: Janssen, Novartis, BMS/Celgene, Amgen, Sanofi, EUSAPharm, Kite/Gilead, Roche, GSK, Medigene; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. W. Alsdorf: Financial Interests, Personal, Advisory Board: Janssen; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH; Financial Interests, Personal, Other, Honoraria/travel costs: Janssen, BioNTech Cell & Gene Therapies GmbH. E. Wagner-Drouet: Financial Interests, Personal, Advisory Board: Novartis, Kite/Gilead, MSD; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. D. Heudobler: Financial Interests, Personal, Advisory Board: BMS, MSD, Janssen-Cilag, Roche, Pfizer, Boehringer-Ingelheim; Financial Interests, Personal, Speaker’s Bureau: BMS, Roche, Pfizer, Novartis; Financial Interests, Institutional, Research Grant: BMS, Janssen-Cilag; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. P. Borchmann: Other, Personal and Institutional, Sponsor/Funding: Takeda Oncology, Novartis, MSD; Other, Personal and Institutional, Principal Investigator: Miltenyi Biotech; Other, Personal, Advisory Board: Roche, Amgen; Other, Personal and Institutional, Advisory Board: Gilead; Other, Personal, Invited Speaker: BMS, Celgene, AbbVie; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. C. Bokemeyer: Financial Interests, Personal, Other, Honoraria: Merck KGaA, Sanofi, Roche, Bayer, Bristol-Myers Squibb, AstraZeneca, Merck Sharp Dohme, Berlin Chemie, Medac; Financial Interests, Personal, Advisory Board: Sanofi, Bayer Schering Pharma, Merck Sharp & Dohme, GSO, AOK Health Insurance, ODC (Oncology drug consult), Janssen-Cilag GmbH; Financial Interests, Institutional, Research Grant: AbbVie, ADC Therapeutics, Agile Therapeutics, Alexion Pharmaceuticals, Amgen, Apellis Pharmaceuticals, Astellas Pharma, AstraZeneca, Bayer, BerGenBio, Blueprint Medicines, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eisai, Gilead Sciences, Glycotope GmbH, GlaxoSmithKline, Incyte, IO Biotech, Isofol Medical, Janssen-Cilag, Karyopharm Therapeutics, Lilly, Millennium, MSD, Nektar, Novartis, Rafael Pharmaceuticals, Roche, Springworks Therapeutics, Taiho Pharmaceutical, BioNTech, Ipsen, Servier/Pfizer, Immatics, CPT Cellex Patient Treatment, Glycostem; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Merck Serono, Sanofi, Bristol-Myers Squibb, Janssen-Cilag; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. S. Klobuch: Non-Financial Interests, Institutional, Funding, Grant support: Neogene Therapeutics; Non-Financial Interests, Personal, Research Grant, Medical writing support: BioNTech Cell & Gene Therapies GmbH. E. Smit: Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. F. Müller: Financial Interests, Institutional, Advisory Board: AstraZeneca, BMS; Financial Interests, Institutional, Other, Honoraria and travel support: AstraZeneca, AbbVie, BMS, Gilead, Janssen, Novartis, Pfizer; Financial Interests, Institutional, Research Grant: Medimmune; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. A. Desuki: Financial Interests, Personal, Advisory Board: Bristol Myers-Squibb, Eisei, MSD, Bayer, Janssen-Cilag; Financial Interests, Personal, Invited Speaker: Pfizer, Bristol Myers-Squibb, Janssen-Cilag; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. F. Lüke: Financial Interests, Personal, Advisory Board: Janssen Cilag, MSD; Financial Interests, Personal, Research Grant, Grant support: Novartis; Financial Interests, Personal, Invited Speaker: Roche; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. E. Wiegert: Financial Interests, Personal, Other, Consultant: BioNTech, Casi, Exicure, InflaRx, iTeos therapeutics, Molecular templates, Pieris, Roche, RS Oncology, Sapience, Vyriad Inc, Schrödinger, Taiho; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. C. Flemmig: Financial Interests, Personal, Full or part-time Employment: BioNTech SE; Financial Interests, Personal, Stocks/Shares: BioNTech SE; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. C. Schulz-Eying: Financial Interests, Personal, Full or part-time Employment: BioNTech SE; Financial Interests, Personal, Stocks/Shares: BioNTech SE; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. B. Rengstl: Financial Interests, Personal and Institutional, Full or part-time Employment: BioNTech SE; Financial Interests, Personal, Stocks/Shares: BioNTech SE; Financial Interests, Personal, Royalties, Holds patents: BioNTech SE; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. L. Preussner: Financial Interests, Personal and Institutional, Full or part-time Employment: BioNTech SE; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. 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; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH. 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, TRON; Financial Interests, Institutional, Funding, TRON receives grant support from Bundesministerium für Bildung und Forshung, DFG, European Commission: TRON; Financial Interests, Personal and Institutional, Leadership Role, Scientific advisor: TRON; Non-Financial Interests, Personal, Funding, Medical writing support: BioNTech Cell & Gene Therapies GmbH.