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
63P - Single-cell RNA-seq combined with bulk RNA-seq revealed the involvement of pancreatic cancer tissue-resident macrophages in tumour progression and the immunotherapy response
Presenter: Bin Wu
Session: Poster Display session
Resources:
Abstract
64P - Gene-editing of T cells to provide resistance against macrophage-mediated suppression: setting up an in vitro model
Presenter: Rui Coelho
Session: Poster Display session
Resources:
Abstract
68P - Real-world outcomes of nivolumab and/or ipilimumab in patients with stage III-IV melanoma, MELIOR study
Presenter: Ainara Soria Rivas
Session: Poster Display session
Resources:
Abstract
69P - Dose-dependent detrimental effect of proton pump inhibitors (PPIs) on clinical outcomes from immune checkpoint inhibitors (ICI) in patients (pts) with solid tumors
Presenter: elena speziale
Session: Poster Display session
Resources:
Abstract
70P - Efficacy of PD-1 blockade plus chemotherapy in patients with oncogenic-driven non-small cell lung cancer
Presenter: Haowei Wang
Session: Poster Display session
Resources:
Abstract
71P - Discontinuation of immune checkpoint inhibitors for reasons other than disease progression and the impact on relapse and survival of advanced melanoma patients: A systematic review and meta-analysis
Presenter: Konstantinos Lallas
Session: Poster Display session
Resources:
Abstract
72P - Concurrent local therapy (CLT) extends clinical benefit of tebentafusp (tebe) in metastatic uveal melanoma (mUM) patients (pts)
Presenter: Tristan Lim
Session: Poster Display session
Resources:
Abstract
73P - Impact of Assessment-to-Treatment Interval on the Predictive Value of PD-L1 Expression in Melanoma
Presenter: Cecilie Vestergaard
Session: Poster Display session
Resources:
Abstract
74P - Real-world impact of adjuvant anti-PD-1 therapy on survival in Danish resected stage III melanoma patients
Presenter: Marie Weitemeyer
Session: Poster Display session
Resources:
Abstract
75P - Real-world data of adebrelimab in the first-line treatment of patients with small cell lung cancer
Presenter: Yong Song
Session: Poster Display session
Resources:
Abstract