Abstract CT274: Individualized APC targeting VB10.NEO cancer vaccines induce broad neoepitope-specific CD8 T cell responses in patients with advanced or metastatic solid tumors: interim results from a phase 1/2a trial
Authors: Krauss Jürgen , Krakhardt Angela , Eisenmann Stephan , Ochsenreither Sebastian , Berg Kaja C.G , Kushekhar Kushi , Fallang Lars-Egil , Pedersen Mikkel W. , Torhaug Siri , Slot Karsten B. , Schjetne Karoline 
Published: April 2023

Abstract
Background: VB N-01 is an open label phase 1/2a basket trial to evaluate safety, feasibility, and immunogenicity of a therapeutic DNA cancer vaccine VB10.NEO in patients with locally advanced or metastatic solid cancers. Each VB10.NEO vaccine contains up to 20 neoepitopes selected by the proprietary AI platform NeoSELECT and is designed to target antigen presenting cells using Nykode’ s modular vaccine platform known as Vaccibody™.
Patients and Methods: The trial enrolled patients with locally advanced or metastatic solid cancers (renal cell carcinoma, urothelial cancer, non-small cell lung cancer, squamous cell carcinoma of the head and neck, and melanoma), who did not obtain complete responses on immune checkpoint inhibitor therapy (CPI). Up to 14 VB10.NEO doses (3 mg per dose) were administered i.m. by PharmaJet Stratis® for up to 1 year in combination with standard of care (CPI and/or other anti-cancer therapies). Blood samples and tumor biopsies were collected at baseline and during treatment for evaluation of immune responses.
Results: At cut-off of May 2022, 41 patients had received at least one vaccination with VB10.NEO. The vaccine was safe and well-tolerated with no new or additional toxicity reported beyond that expected for CPIs alone. All patients displayed immune responses to a minimum of 3 neoepitopes (average 53% of vaccine neoepitopes), assessed by in vitro stimulation (IVS) interferon-gamma ELISpot. T cell responses were elicited in both high and low tumor mutational burden patients (TMB range 2-69mut/Mb). Multiple vaccinations increased the breadth and magnitude of the immune responses with vaccine-induced T cell responses (de novo and/or amplified pre-existing) measured in 95% of eligible patients. IVS intracellular cytokine staining of selected patients demonstrated that the majority of neoepitopes induced polyfunctional CD8 T cells. TCR sequencing of baseline and on-treatment samples (6 patients) showed expansion of T cell clones in both blood and tumor with selected clones being expanded in both compartments.
Conclusions: VB10.NEO was generally well tolerated in patients with various pre-treated and advanced cancers. Assessment of neoepitope-specific T cell reactivity demonstrated VB10.NEO-induced broad and long-lasting T cell responses, and the majority of tested neoepitopes activated polyfunctional CD8 T cells. Pre- and post-vaccination TCRseq analysis of blood and tumor samples demonstrated the presence of blood-expanded clones in the on-treatment tumor sample potentially indicating trafficking of VB10.NEO-expanded T cells to the tumor site.
Citation Format: Jürgen Krauss, Angela Krakhardt, Stephan Eisenmann, Sebastian Ochsenreither, Kaja C.G Berg, Kushi Kushekhar, Lars-Egil Fallang, Mikkel W. Pedersen, Siri Torhaug, Karsten B. Slot, Karoline Schjetne. Individualized APC targeting VB10.NEO cancer vaccines induce broad neoepitope-specific CD8 T cell responses in patients with advanced or metastatic solid tumors: interim results from a phase 1/2a trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT274.