1084P - Phase II study of AI-designed personalized neoantigen cancer vaccine, EVX-01, in combination with pembrolizumab in advanced melanoma

Background

Despite the recent progress in CPI therapy, there remains an unmet need to further improve the outcomes of patients with advanced melanoma. Here, we report 1-year data from a phase II study, assessing safety, efficacy and immunogenicity of the personalized neoantigen (neoAg) peptide vaccine, EVX-01, combined with pembrolizumab in advanced melanoma (NCT05309421).

Methods

Patients (pts) with treatment naïve unresectable or advanced melanoma were enrolled. Pembrolizumab (400mg IV Q6W) was given for 12 wks prior to the first dose of EVX-01. EVX-01 was administered (2mg IM Q2W) for six priming and four booster doses. Investigator response was measured using RECIST 1.1. with scans at baseline and 12 wk intervals thereafter. Primary endpoint, SD to PR/CR or PR to CR conversion rate post EVX-01. Vaccine neoAgs were identified by Evaxion’s target discovery AI-Immunology™ platform using tumor DNA- and RNA-sequencing data. T-cell responses were assessed by IFN-γ ELISpot assay and intracellular cytokine staining.

Results

17 pts were enrolled; response data evaluable for 16. Data cut-off date 07-May-2024 with a med f/u 12.6 mo. PFS was 11.3 mo. At wk 12 post-pembrolizumab only, 8 (50%) PR, 6 (37.5%) SD and 2 (12.5%) PD. 12 pts were evaluable for response at wk 48. 3/12 (25%) had improvement in their response at wk 48 compared to their wk 12 scans; 2 SD pts achieved PR and 1 PR pt achieved CR. 1 PD pt showed 50% tumor RED from wk 12 to wk 72, 21.4% RED from wk 0 and metabolic CR on PET wk 52. EVX-01 induced neoAg-specific T-cell responses in all pts receiving all priming doses, with an observed T-cell reactivity against the majority of the EVX-01 neoAgs. This demonstrates the ability of the AI-Immunology™ platform to precisely predict effective vaccine targets. Treatment emergent adverse events (TEAEs) with EVX-01 were primarily G1/2 and included inj. site reaction (4.8%), diarrhea (4.0%), rash (2.4%), fatigue (1.6%), and one G3 TEAE, hepatitis. No additional toxicity was observed with the combination.

Conclusions

The AI-Immunology™ platform predicted tumor-specific neoAgs with a high success rate. Our results indicate that EVX-01 holds promise as a safe and effective therapeutic approach when used in combination with anti-PD1 therapy.

Clinical trial identification

NCT05309421; 09-Feb-2023.

Editorial acknowledgement

Legal entity responsible for the study

Evaxion Biotech A/S.

Funding

Evaxion Biotech A/S.

Disclosure

M.A.A. Khattak: Financial Interests, Personal and Institutional, Local PI, Presenting author of this abstract and previous. I could not retreive information through DOI. But Dr. Khattak has filled out via system: ID 48839: Evaxion Biotech A/S. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, Novartis, Merck Serono, Sun Pharma, Sanofi, Sandoz, Immunocore, Boehringer Ingelheim Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant, Advisory Role and Travel support: MSD, Pierre Fabre; Financial Interests, Personal, Other, Consultant and Advisory Role.Travel support: Pfizer/Array; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Consultant Role: Pfizer, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna; Financial Interests, Personal, Other, Consultant role and travel support: Bio-AI Health; Financial Interests, Personal, Advisory Board, Consultant and Advisory role: ValoTx; Financial Interests, Personal, Advisory Board, Consultant and Advisor role.Travel support: Replimmune; Financial Interests, Personal, Advisory Board, Advisor role: Bayer; Financial Interests, Personal, Other, Consultant and Advisory: Erasca; Financial Interests, Personal, Other, Consultant: Philogen; Financial Interests, Personal, Advisory Board: BionTech, Anaveon; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Member of Board of Directors, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR. P. Queirolo: Financial Interests, Personal, Speaker, Consultant, Advisor: BMS, Pierre Fabre, MSD, Novartis, Sun Pharma, Regeneron, Immunocore; Financial Interests, Personal, Speaker, Consultant, Advisor, Evaxion Biotech A/S: Merck; Financial Interests, Personal and Institutional, Principal Investigator: Evaxion Biotech A/S. M. Chisamore: Financial Interests, Institutional, Full or part-time Employment: Merck & Co. Inc; Financial Interests, Institutional, Stocks/Shares: Merck & Co. Inc. D. Kleine-Kohlbrecher, M. Lausen, N. Viborg, M. A. Pavlidis, R. O. Andersen, S. F. Thorsen: Financial Interests, Personal, Full or part-time Employment: Evaxion Biotech A/S. T. S. Jepsen, T. Trolle, B. Rønø: Financial Interests, Personal, Full or part-time Employment: Evaxion Biotech A/S; Financial Interests, Personal, Stocks/Shares: Evaxion Biotech A/S. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, AstraZeneca UK Limited, Bayer Healthcare Pharmaceuticals, BioNTech SE, Boehringer Ingelheim Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG, Highlight Therapeutics S.L, IOBiotech, Immunocore Ireland Limited, Innovent Bioilogics USA Inc, Merck Sharp & Dohme, Novartis Pharma AG, PHMR Limited, Pierre Fabre, Regeneron Pharmaceuticals Inc, Scancell Limited, SkylineDX B.V; Non-Financial Interests, Principal Investigator, GL is PI on over 30 clinical trials: GL is PI on over 30 clinical trials.