A phase I/II study of HB-201, an arenavirus-based cancer immunotherapy, alone, or in combination with anti-PD-1 in patients with HPV16+ cancers.

Background: Human Papillomavirus 16 (HPV16) is linked to several cancer types; 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 can also serve as immunogenic tumor-associated antigens. HB-201 is a replication-competent live-attenuated vector based on the arenavirus LCMV encoding a non-oncogenic E7 and E6 fusion protein. In preclinical models, both intravenously (IV) and intratumorally (IT) administered HB-201 demonstrate potent immunogenicity by induction of HPV16-specific cytotoxic T cells and associated efficacy. Methods: This is a first in human, Phase I/II study of HB-201 monotherapy or in combination with PD-1 immune checkpoint inhibitor (anti-PD-1) in HPV16+ confirmed recurrent/metastatic cancers. Phase I consists of 2 treatment groups, each conducted with a 3+3 dose escalation design. Group 1 is enrolling patients with HPV16+ head and neck squamous cell carcinoma who will receive HB-201 IV only. Group 2 is enrolling HPV16+ cancer patients with a safely accessible tumor site who will receive HB-201 IT for the first dose, followed by HB-201 IV for subsequent doses (IT-IV). HB-201 will be administered every 21 days. The Phase II component will be conducted with the recommended Phase II doses (RP2Ds) defined in Phase I and will consist of 3 groups: Group A (HB-201 IV only), Group B (HB-201 IV plus anti-PD-1), and Group C (HB-201 IT-IV). Key eligibility criteria include age \u3e 18, ECOG performance status 0-1, confirmed HPV16+ recurrent or metastatic cancer, disease progression from at least 1 systemic standard of care therapy, and measurable disease per RECIST v1.1. The Phase I primary objective is to determine RP2Ds for IV and IT HB-201. The Phase II primary objective is to assess antitumor activity. Secondary endpoints for both phases include safety, tolerability, overall survival, progression-free survival, and duration of response. Exploratory objectives include characterization of immunogenicity of HB-201 and biomarkers associated with immune or antitumor response. Enrollment to Groups 1 and 2 began in December 2019. Clinical trial information: NCT04180215