Methods

This is an open-label, multicenter, 2-part, randomized Phase I/II study (NCT02291055). Patients (≥18 years) with squamous/nonsquamous cervical carcinoma or HPV-associated squamous cell cancer of the head and neck who progressed on ≥1 prior platinum-based therapy in the recurrent/metastatic setting are eligible. The primary objective of Phase I is to evaluate the safety and tolerability of ADXS11-001 plus MEDI4736 and select a recommended Phase II dose (RP2D) for the combination. The primary objective of Phase II is to evaluate the tumor response, progression-free survival (PFS), and safety of ADXS11-001 and MEDI4736 as monotherapy and in combination. Exploratory objectives for both phases will evaluate associations between biomarkers of immunologic response with tumor response and PFS. In Phase I, up to 18 patients will receive a fixed dose of ADXS11-001 (1×10⁹ colony-forming units [CFU]), while the dose of MEDI4736 will be escalated (starting at 3 mg/kg) according to a standard 3+3 design. In Phase II, patients (n≈48) will be randomized (1:1:2) to receive either ADXS11-001 (1×10⁹ CFU) or MEDI4736 (10 mg/kg) or both at the RP2D; all treatment arms will be stratified by disease. In both phases, ADXS11-001 will be administered every 4 weeks and MEDI4736 every 2 weeks. Patients will receive treatment up to 1 year or until they discontinue due to disease progression or unacceptable toxicity. Efficacy parameters will be evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) and immune-related RECIST criteria, and safety determined using the Common Terminology Criteria for Adverse Events (CTCAE). Enrollment for this study is anticipated in July 2015.