A Study of ADXS11-001 or MEDI4736 Alone or Combination In Cervical or Human Papillomavirus (HPV)+ Head & Neck Cancer

Phase 1-2 Study of ADXS11-001 or MEDI4736 Alone or Combination In Previously Treated Locally Advanced or Metastatic Cervical or HPV+ Head & Neck Cancer

This was a multicenter, open-label, 2-part randomized study of MEDI4736 administered as monotherapy or in combination with ADXS11-001 to participants with recurrent/persistent or metastatic squamous or non-squamous carcinoma of the cervix or metastatic human papillomaviruses (HPV)+ squamous cell carcinoma of the head and neck (SCCHN).

The study was conducted in 2 parts Part A (dose-escalation and expansion) and Part B (expansion).

Part A:

Part A of the study was a Phase 1 dose escalation evaluation of the combination treatment of ADXS11-001 at a fixed dose of 1×10^9 colony-forming units (CFU) administered intravenously (IV) every 4 weeks (Q4W) and escalating doses of MEDI4736 (3 mg/kg and 10 mg/kg) administered IV every 2 weeks (Q2W) to determine the safety and tolerability of the combination and to identify a recommended Phase 2 dose (RP2D). Part A also included an expansion cohort of participants with metastatic SCCHN only. Once the RP2D was identified, the expansion cohort of Part A of the study were to commence.

Part B:

Part B of the study was a Phase 2 design in which participants who had failed at least 1 prior systemic treatment for their recurrent, persistent or metastatic cervical cancer were enrolled and randomized 1:1 to receive either MEDI4736 10 mg/kg alone or MEDI4736 10 mg/kg in combination with ADXS11-001 1×10^9 CFU.

Inclusion Criteria:

1. Have histological diagnosis of SCCHN with confirmation of HPV positivity or squamous, non-squamous, adenosquamous, carcinoma or adenocarcinoma of the cervix which HPV positivity is not required
2. Have measurable and/or evaluable disease by response evaluation criteria in solid tumors (RECIST) 1.1
3. Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
4. Have adequate organ function defined by the protocol.

Exclusion Criteria:

1. Has any prior Grade ≥3 immune-related adverse event (irAE) while receiving immunotherapy, including anti-CTLA-4 treatment, or any unresolved irAE >Grade 1.
2. Has a diagnosis of immunodeficiency or is receiving any systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to Day 1 of trial treatment.
3. Has any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for invasive malignancy within 2 years. Concurrent use of hormones for non-cancer-related conditions (eg, insulin for diabetes and hormone replacement therapy) is acceptable.
4. Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents.
5. Has implanted medical device(s) that pose a high risk for colonization and/or cannot be easily removed (e.g., prosthetic joints, artificial heart valves, pacemakers, orthopedic screw(s), metal plate(s), bone graft(s), or other exogenous implant(s)). NOTE: More common devices and prosthetics which include arterial and venous stents, dental and breast implants, and venous access devices (e.g., Port-a-Cath or Mediport) are permitted. Sponsor must be contacted prior to consenting any subject who has any other device and/or implant