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.
Resources from the same session
53P - Novel ex-vivo manufacturing of transiently expressed armoured CAR T cells for glioblastoma
Presenter: Saket Srivastava
Session: Poster Display session
Resources:
Abstract
54P - Superior antitumor activities of fourth-generation CAR-T cells containing three costimulatory domains targeting GD2-positive tumors
Presenter: Jatuporn Sujjitjoon
Session: Poster Display session
Resources:
Abstract
55P - Engineering of chimeric cytokine receptors (CCR) to induce IL-7 signaling to CAR-T cells for solid tumor treatment
Presenter: Marta Soria Castellano
Session: Poster Display session
Resources:
Abstract
56P - Potent antitumor efficiency of CD19-CAR T cells self-secreting PD-L1 x CD3 BiTE against aggressive B-cell lymphoma
Presenter: Jatuporn Sujjitjoon
Session: Poster Display session
Resources:
Abstract
57P - SENDER™ Directed LNP Delivery of mRNA for In Situ generation of highly potent CAR T Cells
Presenter: Biao Ma
Session: Poster Display session
Resources:
Abstract
58P - Cardiovascular outcomes of novel CAR-T cell therapies: A meta-analysis of incidence, risk factors, and management of cardiotoxicity
Presenter: Hashim Talib Hashim
Session: Poster Display session
Resources:
Abstract
59P - Long term survival data from all recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients treated with MVX-ONCO-1 during open-labelled phase I and phase IIa clinical trials
Presenter: Nicolas Mach
Session: Poster Display session
Resources:
Abstract
60P - Innovative applications of neoantigens in dendritic cell-derived exosome (DEX) therapy and their impact on personalized cancer treatment
Presenter: Ramon Gutierrez
Session: Poster Display session
Resources:
Abstract
61P - Optimized protocol for the accelerated production of dendritic cell-derived exosomes (DEXs): Achieving speed without compromising efficacy
Presenter: Ramon Gutierrez
Session: Poster Display session
Resources:
Abstract
62P - Ecto-CRT induction of NKp46 surface expression increases osimertinib-resistant lung cancer’s sensitivity to NK cells
Presenter: Sumei Chen
Session: Poster Display session
Resources:
Abstract