Abstract CT187: Immunogenicity of the therapeutic HPV16-specific cancer vaccine abipapogene suvaplasmid (VB10.16) in combination with pembrolizumab given as 1L treatment for HPV16+ PD-L1+ r/m oropharyngeal cancer: Preliminary results from phase 1 of

Abstract Background: Improved therapeutic options are warranted for patients with HPV16+, PD-L1+, unresectable recurrent or metastatic (r/m) oropharyngeal cancer (OPC). Therapeutic cancer vaccines targeting the HPV16 oncoproteins E6 and E7 have potential to elicit and enhance antigen-specific T cell responses to HPV16-positive cancer cells and may improve patient outcome. Abipapogene suvaplasmid (abi-suva; VB10.16) is a DNA-based therapeutic cancer vaccine, which has shown promising clinical efficacy in combination with atezolizumab in heavily pretreated HPV16+ r/m cervical cancer.1 In the ongoing phase 1/2 VB C-03 trial (NCT06016920), abi-suva is tested in combination with pembrolizumab in HPV16+, PD-L1+ r/m OPC in the first-line (1L) setting. All dose levels have been safety-cleared, treatment has been shown to be well-tolerated, and the ORR for phase 1 was 38.5% (5/13)2. Here we report pre-specified immunogenicity results from the phase 1 (dose escalation) of the VB C-03 trial. Methods: The primary endpoint in the phase 1 dose escalation was to safety-clear abi-suva doses ≥ 3 mg and select the recommended phase 2 dose. Assessment of immunogenicity was a secondary endpoint, and anti-tumor activity and clinical efficacy were exploratory endpoints. Ex vivo ELISpot data from 9 patients available at the time of analysis is presented, in addition to preliminary TCR sequencing data from 12 patients. Results: A total of 13 patients (all male, median age 64 years) received 3 mg (n=1), 6 mg (n=6) and 9 mg (n=6) abi-suva plus pembrolizumab in the phase 1. Ex vivo IFN-γ ELISpot analyses showed rapid, strong and durable antigen-specific T cell responses. All analyzed patients in the 6 mg (n=4) and 9 mg (n=4) cohorts showed a >2-fold vaccine-induced T cell response, in contrast to the 3 mg patient. In-depth analyses of the T cell expansion by longitudinal TCR sequencing supported the rapid and durable expansion, also on the level of individual T cell clonotypes. A median of 85 clones were expanded during treatment, of which a median of 45 clones were de novo (n=12 patients). Together these results support that the treatment both reinvigorated pre-existing clonotypes and induced expansion of de novo clonotypes. Conclusion: Treatment with abi-suva plus pembrolizumab successfully induced HPV16-specific T cell responses in a majority of the patients in the phase 1 of the VB C-03 trial. TCR sequencing further supported durable T cell expansion and emergence of de novo clones. Together with the clinical data from phase 1 of the VB C-03 trial, these data support the ability of abi-suva to induce clinically meaningful T cell responses. References: 1. Hillemanns, P. et al. Safety and efficacy of the therapeutic DNA-based vaccine VB10.16 in combination with atezolizumab in persistent, recurrent or metastatic HPV16-positivecervical cancer: a multicenter, single-arm phase 2a study. J. Immunother. Cancer 13, e010827 (2025). 2. Even, C. et al. ICHNO 2026 Citation Format: CCaroline Even, Saira Khalique, Marc B. Oliva, Marie Vinches, Marta G. Arnau, Kaja C. Berg, Ingvild S. Leikfoss, Aleksandra Urban, Marthe J. Jørgensen, Christian W. Wold, Judith Wong, Miriam Ragle Aure, Lena Finnesand, Roberto Oliveri, Agnete B. Fredriksen, Åse Bratland. Immunogenicity of the therapeutic HPV16-specific cancer vaccine abipapogene suvaplasmid (VB10.16) in combination with pembrolizumab given as 1L treatment for HPV16+ PD-L1+ r/m oropharyngeal cancer: Preliminary results from phase 1 of the VB-C-03 trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT187.