160P - Oral DNA vaccination targeting personalised neoantigens in immune checkpoint-inhibitor treated solid tumor patients: Interim results

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.