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

NCT ID: NCT02291055

Last Updated: 2023-03-20

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-04-30
• Study Completion Date: 2020-11-20

Brief 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).

Detailed Description

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.

Conditions

Cervical Cancer; Cancer; Head and Neck Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A Escalation (Cervical): 1×10^9 CFU ADXS11-001/ 3 mg/kg MEDI4736

Participants with cervical cancer received MEDI4736 3 milligrams per kilogram (mg/kg) intravenous (IV) infusion every 2 weeks (Q2W) at an infusion rate of approximately 60 minutes followed by ADXS11-001 1×10\^9 CFU IV infusion every 4 weeks (Q4W) at an infusion rate of approximately 60 minutes. Treatment cycles were 8-week in duration and participants were to continue therapy for up to 1 year or until documented progression, unacceptable toxicity, withdrawal of consent, or other treatment discontinuation criteria were met.

Group Type: EXPERIMENTAL

ADXS11-001

Intervention Type: DRUG

MEDI4736

Intervention Type: DRUG

Part A Escalation (Cervical and Head and Neck): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736

Participants with cervical cancer and SCCHN received MEDI4736 10 mg/kg IV infusion Q2W at an infusion rate of approximately 60 minutes followed by ADXS11-001 1×10\^9 CFU IV infusion Q4W at an infusion rate of approximately 60 minutes. Treatment cycles were 8-week in duration and participants were to continue therapy for up to 1 year or until documented progression, unacceptable toxicity, withdrawal of consent, or other treatment discontinuation criteria were met.

Group Type: EXPERIMENTAL

ADXS11-001

Intervention Type: DRUG

MEDI4736

Intervention Type: DRUG

Part A Expansion (Head and Neck): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736

Participants with SCCHN received MEDI4736 10 mg/kg IV infusion Q2W at an infusion rate of approximately 60 minutes followed by ADXS11-001 1×10\^9 CFU IV infusion Q4W at an infusion rate of approximately 60 minutes. Treatment cycles were 8-week in duration and participants were to continue therapy for up to 1 year or until documented progression, unacceptable toxicity, withdrawal of consent, or other treatment discontinuation criteria were met.

Group Type: EXPERIMENTAL

ADXS11-001

Intervention Type: DRUG

MEDI4736

Intervention Type: DRUG

Part B Expansion (Cervical): 10 mg/kg MEDI4736

Participants with cervical cancer received MEDI4736 10 mg/kg IV infusion Q2W at an infusion rate of approximately 60 minutes. Treatment cycles were 8-week in duration and participants were to continue therapy for up to 1 year or until documented progression, unacceptable toxicity, withdrawal of consent, or other treatment discontinuation criteria were met.

Group Type: EXPERIMENTAL

MEDI4736

Intervention Type: DRUG

Part B Expansion (Cervical): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736

Participants with cervical cancer received MEDI4736 10 mg/kg IV infusion Q2W at an infusion rate of approximately 60 minutes followed by ADXS11-001 1×10\^9 CFU IV infusion Q4W at an infusion rate of approximately 60 minutes. Treatment cycles were 8-week in duration and participants were to continue therapy for up to 1 year or until documented progression, unacceptable toxicity, withdrawal of consent, or other treatment discontinuation criteria were met.

Group Type: EXPERIMENTAL

ADXS11-001

Intervention Type: DRUG

MEDI4736

Intervention Type: DRUG

Interventions

ADXS11-001

Intervention Type: DRUG

MEDI4736

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

MedImmune LLC

INDUSTRY

Sponsor Role: collaborator

Advaxis, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Site

Los Angeles, California, United States

Site

New Haven, Connecticut, United States

Site

Jacksonville, Florida, United States

Site

Miami, Florida, United States

Site

Tampa, Florida, United States

Site

Urbana, Illinois, United States

Site

Lexington, Kentucky, United States

Site

Baltimore, Maryland, United States

Site

Detroit, Michigan, United States

Site

Omaha, Nebraska, United States

Site

Brooklyn, New York, United States

Site

New York, New York, United States

Site

Canton, Ohio, United States

Site

Hilliard, Ohio, United States

Site

Oklahoma City, Oklahoma, United States

Site

Chattanooga, Tennessee, United States

Site

Milwaukee, Wisconsin, United States

Countries

United States

References

Slomovitz BM, Moore K, Vangala S, Parsi M, Sheerie S, John Heyburn J ,Posner M. Phase II study of durvalumab alone or in combination with ADXS11-001 (AXAL) in recurrent/persistent or metastatic cervical cancer. Annual Meeting on Women's Cancer. March 28-31, 2020. Toronto Canada.

Reference Type: RESULT

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

ADXS001-04

Identifier Type: -

Identifier Source: org_study_id