Phase II Trial of MEDI0457 and Durvalumab for Patients with Recurrent/metastatic HPV-associated Cancers.

2595 Background: Infection with human papillomavirus (HPV) types 16 or 18 drives oncogenesis for the majority of patients (pts) with cervical, anal, and some penile cancers via viral oncoproteins E6 and E7. While anti-PD1/PD-L1 antibodies have activity in pts with HPV-associated cancers, the majority do not derive benefit from these agents as monotherapy. MEDI0457, a therapeutic DNA vaccine containing plasmids for E6 and E7 oncogenes for HPV-16/18 and IL-12 adjuvant, has been shown to be safe and to provoke an immune response against the expressed antigens. We tested MEDI0457 with the anti-PD-L1 antibody durvalumab for pts with recurrent or metastatic HPV-associated cancers with the goal of improving anti-tumor activity. Methods: Pts with HPV-16/18 cervical cancer or rare (anal, penile, vaginal, or vulvar) HPV- associated cancers that were recurrent and/or metastatic following standard therapies were eligible. No prior immunotherapy was allowed. Pts received 7 mg of MEDI0457 intramuscularly (weeks 1, 3, 7, 12, and every 8 weeks thereafter) and durvalumab 1500 mg intravenously every 4 weeks starting at week 4. The primary endpoint was best overall response according to RECIST 1.1. Adverse events (AE) were assessed using CTCAE v4.03. A Simon two-stage phase 2 trial (Ho: p