a study of adxs11-001 or medi4736 alone or combination in cervical or human papillomavirus (hpv)+ head & neck cancer

Conditions: Cervical Cancer; Cancer; Head and Neck Cancer

Summary: 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.

Eligibility criteria:
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