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-gamma 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-positive cervical cancer: a multicenter, single-arm phase 2a study. J. Immunother. Cancer 13, e010827 (2025). 2. Even, C. et al . ICHNO 2026