The ESMO abstract
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.
