Abstract LB049: Preliminary analysis of immunogenicity of HB-201 and HB-202, an arenavirus-based cancer immunotherapy, in patients with advanced HPV16-positive cancers

Background: Human Papillomavirus 16 (HPV16) is linked to most HPV-associated cancers such as cervical, head and neck, vaginal and anal cancers. Treatment options are limited for patients with HPV16+ recurrent or metastatic cancers. The generation and maintenance of the HPV16+ malignant state requires the stable expression of HPV16-specific E7 and E6 oncogenes, which therefore constitute attractive targets for immunotherapy. HB-201 and HB-202 are both replicating live-attenuated vectors based on arenaviruses LCMV and PICV, respectively, expressing the same non-oncogenic HPV16 E7E6 fusion protein for induction of tumor specific T-cell responses. In preclinical models, administration of HB-201 alone and sequential administration of HB-202 followed by HB-201 was safe and demonstrated potent immunogenicity by induction of E7 and E6 -specific CD8+ T cell responses and efficient tumor control of HPV+ TC-1 tumors. Methods: A first-in-human, Phase I/II open-labelled clinical trial of HB-201 single vector therapy and HB-201 & HB-202 two-vector therapy in patients with treatment-refractory HPV16+ cancers is currently ongoing (NCT04180215). Here, we present first immunogenicity results from the dose escalation phase I of this study. The phase I of the trial is designed to evaluate different dose levels and dosing schedules of HB-201 as a single-vector therapy or as an alternating two-vector therapy together with HB-202. Peripheral blood mononuclear cells (PBMCs) were collected before and after treatment from all patients. PBMCs from a subset of patients were examined for HPV16-specific T cell responses measured by IFN-γ enzyme-linked immunospot. Paired tissue biopsy and serum samples were also collected and being currently evaluated for histology and pharmacokinetics. Results: We demonstrated induction of a directly ex vivo (i.e. no expansion) detectable HPV16-specific T-cell response in PBMCs from patients receiving a single dose of HB-201 or HB-202. Additional exploratory analysis will be available at the time of the meeting. Conclusion: These preliminary data demonstrate for the first time with arenavirus vectors, the induction of HPV16-specific T cells in cancer patients following a single injection of HB-201 or HB-202. Arenavirus vectors expressing E7E6 may constitute a new potential therapy for patients with treatment refractory HPV16+ cancers. Clinical data will be presented in an upcoming scientific meeting. Additional schedules, alternating two-vector therapy