1017O - NTC-001: A phase I study to test safety and efficacy of BNT221, a non-engineered neoantigen-specific T cell product, in patients with advanced or metastatic melanoma

Background

Neoantigens are tumor-specific antigens derived from somatic mutations and have been shown to elicit antitumor immune responses. The interim results of a phase I study (NCT04625205) testing a personalized, non-engineered, neoantigen-specific T cell product (BNT221) targeting multiple neoantigens are presented.

Methods

Nine patients with checkpoint- and, if applicable, BRAFi-resistant metastatic melanoma were treated with BNT221. Up to sixty immunogenic MHCI- and MHCII-restricted neoantigens were selected using our RECON® bioinformatics platform and used in an ex vivo induction process (NEO-STIM™) to prime, activate and expand memory and de novo T-cell responses from both the CD4⁺ and the CD8⁺ T cell compartment, using PBMCs collected via leukapheresis. Two BNT221 doses (≥ 1 × 10⁸ cells to ≤ 1 × 10⁹ cells and >2 × 10⁹ cells to ≤ 1 × 10¹⁰ cells) were evaluated in a 3+3 escalation design, with primary (safety and determination of highest tolerable dose), secondary (efficacy, per RESIST 1.1) and exploratory endpoints. Patients were treated with lymphodepleting chemotherapy prior to infusion. Peripheral blood and biopsies were collected for immune monitoring.

Results

BNT221 was well-tolerated. No dose-limiting toxicities were observed, with grade 3-4 toxicities post infusion limited to hematologic toxicities from lymphodepletion. Seven patients showed stable disease as best overall response (12-36+ weeks). Of those, two patients showed tumor reductions at cutaneous and visceral disease sites and reported quality of life improvements. For all patients, drug products were generated with multiple neoantigen specific CD8+ and CD4+ T cell responses, also detected up to 6 weeks post infusion. Evidence of tumor infiltration was observed through TCR sequencing analysis in one patient tested.

Conclusions

In this first in human study, BNT221 as a single infusion therapy demonstrated a tolerable safety profile, product persistence, prolonged stable disease, and tumor regressions in patients with checkpoint inhibitor-resistant metastatic melanoma. Additional study is warranted and BNT221 combination with anti-PD-1 is currently underway.

Clinical trial identification

NCT04625205 November 12th 2020.

Editorial acknowledgement

Legal entity responsible for the study

BioNTech US.

Funding

BioNTech US.

Disclosure

J.S..W. Borgers: Non-Financial Interests, Institutional, Other, Study coordinator/Sub-Investigator: BioNTech US. D. Lenkala, B. McCarthy, V. Kohler, S. Hymson, K. Esaulova, K. Balogh: Financial Interests, Personal, Full or part-time Employment: BioNTech US; Financial Interests, Personal, Stocks/Shares: BioNTech US. O. Finney: Financial Interests, Personal, Full or part-time Employment: BioNTech US; Financial Interests, Personal, Stocks/Shares: blubird bio, 2seventy bio, BioNTech US. S. Klobuch: Financial Interests, Institutional, Advisory Board: Regeneron; Financial Interests, Institutional, Local PI: Neogene. C. Nijenhuis: Non-Financial Interests, Institutional, Other, Production pharmacist: BioNTech US. R.B. Gaynor: Financial Interests, Personal and Institutional, Full or part-time Employment: BioNTech US; Financial Interests, Personal, Stocks/Shares: BioNTech US; Financial Interests, Personal, Member of Board of Directors: Alkermes plc, Infinity Pharmaceuticals, Zai Laboratory; Financial Interests, Personal, Advisory Board: Leap Therapeutics; Financial Interests, Personal, Speaker, Consultant, Advisor: Third Rock Ventures. M. DeMario: Financial Interests, Personal, Full or part-time Employment: BioNTech US; Financial Interests, Personal, Stocks/Shares: BioNTech US. 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, Other, Editor-in-Chief IOTECH: ESMO; Other, Other, Editorial Board ESMO Open: ESMO; Other, Other, Editorial Board: Kidney Cancer. M.M. van Buuren: Financial Interests, Personal, Full or part-time Employment: BioNTech US; Financial Interests, Personal, Stocks/Shares: BioNTech US.