Abstract 160P
Background
Personalised neoantigens serve as promising targets for neoantigen-primed T-cells. NECVAX-NEO1, an oral DNA vaccine, encodes for a series of neoantigens identified and ranked by the artificial intelligence based NEC Immune Profiler software from the patient’s tumor biopsy. Delivered orally by the bacterial Ty21a carrier, a first-in-human basket trial in immune checkpoint inhibitor (CPI)-treated solid tumors aims to assess safety, immunogenicity, biomarker changes, and clinical efficacy.
Methods
In a multicentre, single arm phase I basket study (EudraCT 2021-000607-20) of CPI-treated solid tumor, 5 patients with melanoma, renal cell cancer, or head and neck cancer were treated by NECVAX-NEO1. At enrolment patients were on standard of care CPI treatment for at least 3 months showing either stable disease (SD) or partial response (PR). NECVAX-NEO1 is administered on day 1, 3, 5, 7 with boosting every 4 weeks up to week 24, followed by 2 years of observation. Endpoints include safety and tolerability, ORR, clinical response based on RECIST 1.1 criteria, immune response by ELISpot, tumor tissue evaluation, ctDNA assessments.
Results
The NECVAX-NEO1 safety run-in phase at 107 dosing was completed with 3 patients, showing no treatment-related toxicities and allowing for a dose increase to 108 CFU for subsequent patients. Sixty eight percent of the neoepitopes induced an ELISpot response in patients. All patients experienced de novo polytope responses to targeted neoepitopes with 2 out of 5 patients (40%) showing significantly increased neoantigen-specific signals after vaccination. Higher-ranked epitopes showed higher immune response in responder patients. Four out of five patients experienced stable disease after 24 weeks of treatment corresponding to an 80% disease control rate (DCR). Neoantigen-specific ctDNA profiles aligned with ELISpot responses in the melanoma patient.
Conclusions
The NECVAX-NEO1 treatment showed no toxicity and allowed dose escalation. 68% of neoepitopes induced immune response with 40% of patients displaying significant neoantigen-specific responses and 80% showed disease control rate after 24 weeks of treatment.
Clinical trial identification
NCT05354323.
Legal entity responsible for the study
NEC Bio Therapeutics GmbH, Mannheim, Germany.
Funding
NEC Bio Therapeutics GmbH, Mannheim, Germany.
Disclosure
All authors have declared no conflicts of interest.
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