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

• ClinicalTrials.gov Identifier: NCT02291055
• Recruitment Status: Terminated
• First Posted: November 14, 2014
• Results First Posted: March 20, 2023
• Last Update Posted: March 20, 2023
• Sponsor: Advaxis, Inc.
• Collaborator: MedImmune LLC
• Information provided by (Responsible Party): Advaxis, Inc.

Tracking Information

• First Submitted Date: November 6, 2014
• First Posted Date: November 14, 2014
• Results First Submitted Date: February 20, 2023
• Results First Posted Date: March 20, 2023
• Last Update Posted Date: March 20, 2023
• Actual Study Start Date: April 2015
• Actual Primary Completion Date: July 9, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 20, 2023)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B [ Time Frame: From first dose until 30 days after last dose (maximum duration: 98 weeks) ]
  An adverse event (AE) was any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. Any worsening (ie, any clinically significant adverse change in frequency and/or intensity) of a preexisting condition that was temporally associated with the use of the Sponsor's product, was also considered an AE. A serious adverse event (SAE) was any AE that: results in death; life threatening; resulted in or prolonged an existing inpatient hospitalization, persistent or significant disability/incapacity; congenital anomaly; a new cancer; associated with an overdose; another important medical event. Treatment emergent was defined as events with onset dates on or after the first dose of study medication and within 30 days following the last dose of study medication.
• Progression Free Survival (Part A and Part B): Cervical Cancer Population [ Time Frame: From randomization until objective tumor progression or death (maximum duration: 146 weeks) ]
  Progression-free survival (PFS) was defined as the time from randomization until objective tumor progression based on response evaluation criteria in solid tumors (RECIST) version 1.1 or death. The progressive disease is defined at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. Participants who had not experienced disease progression or who were still alive at the time of evaluation were censored for the analysis. The PFS was estimated using Kaplan-Meier method.
• Progression Free Survival (Part A): Human Papillomavirus (HPV)+ Head and Neck Cancer Population [ Time Frame: From randomization until objective tumor progression or death (maximum duration: 146 weeks) ]
  PFS was defined as the time from randomization until objective tumor progression based on RECIST version 1.1 or death. The progressive disease is defined at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum longest diameter recorded since the treatment started, the appearance of one or more new lesions, or unequivocal progression of existing non-target lesions. Participants who had not experienced disease progression or who were still alive at the time of evaluation were censored for the analysis. The PFS was estimated using Kaplan-Meier method.
• Percentage of Participants With Objective Response as Per RECIST Criteria (Part A and Part B): Cervical Cancer Population [ Time Frame: From randomization until objective tumor progression or death (maximum duration: 146 weeks) ]
  The objective response is defined as confirmed complete response (CR) or partial response (PR) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 millimeter (mm). The PR is defined as >= 30% decrease in the sum of the longest diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions.
• Percentage of Participants With Objective Response as Per RECIST Criteria (Part A): HPV+ Head and Neck Cancer Population [ Time Frame: From randomization until objective tumor progression or death (maximum duration: 146 weeks) ]
  The objective response is defined as confirmed CR or PR based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. The PR is defined as >= 30% decrease in the sum of the longest diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions.
• Percentage of Participants With Objective Response as Per irRECIST Criteria (Part A and Part B): Cervical Cancer Population [ Time Frame: From randomization until objective tumor progression or death (maximum duration: 146 weeks) ]
  The objective response is defined as confirmed CR or confirmed PR based on immune-related RECIST (irRECIST) v1.1 guidelines. The irCR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The irPR is defined as >= 30% decrease in tumor burden compared with baseline.
• Percentage of Participants With Objective Response as Per irRECIST Criteria (Part A): HPV+ Head and Neck Cancer Population [ Time Frame: From randomization until objective tumor progression or death (maximum duration: 146 weeks) ]
  The objective response is defined as confirmed CR or confirmed PR based on irRECIST v1.1 guidelines. The irCR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The irPR is defined as >= 30% decrease in tumor burden compared with baseline.
• Percentage of Participants With Disease Control as Per RECIST Criteria (Part A and Part B): Cervical Cancer Population [ Time Frame: From randomization until objective tumor progression or death (maximum duration: 146 weeks) ]
  The DCR is defined percentage of participants with CR, PR, or stable disease (SD) based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. The PR is defined as >= 30% decrease in the sum of the longest diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the study treatment started. The PD is defined as at least 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
• Percentage of Participants With Disease Control as Per RECIST Criteria (Part A): HPV+ Head and Neck Cancer Population [ Time Frame: From randomization until objective tumor progression or death (maximum duration: 146 weeks) ]
  The DCR is defined percentage of participants with CR, PR, or SD based on RECIST v1.1 guidelines. The CR is defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. The PR is defined as >= 30% decrease in the sum of the longest diameter of all target lesions compared with baseline, in absence of new lesions or unequivocal progression of non-target lesions. The SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum longest diameter since the study treatment started. The PD is defined as at least 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression.
• Percentage of Participants With Disease Control as Per irRECIST Criteria (Part A and Part B): Cervical Cancer Population [ Time Frame: From randomization until objective tumor progression or death (maximum duration: 146 weeks) ]
  The DCR is defined percentage of participants with irCR, irPR, or irSD based on irRECIST v1.1 guidelines. The irCR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The irPR is defined as >= 30% decrease in tumor burden compared with baseline. The irSD is defined as neither a 30% decrease in tumor burden compared with baseline nor a 20% increase compared with nadir can be established.
• Percentage of Participants With Disease Control as Per irRECIST Criteria (Part A): HPV+ Head and Neck Cancer Population [ Time Frame: From randomization until objective tumor progression or death (maximum duration: 146 weeks) ]
  The DCR is defined percentage of participants with irCR, irPR, or irSD based on irRECIST v1.1 guidelines. The irCR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The irPR is defined as >= 30% decrease in tumor burden compared with baseline. The irSD is defined as neither a 30% decrease in tumor burden compared with baseline nor a 20% increase compared with nadir can be established.
• Overall Survival: Cervical Cancer Population [ Time Frame: From first dose until death (maximum duration: 146 weeks) ]
  Overall survival is defined as the time from the date of start of study treatment until death due to any cause. Any participant not died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The OS was estimated using Kaplan-Meier method.
• Overall Survival: HPV+ Head and Neck Cancer Population [ Time Frame: From first dose until death (maximum duration: 146 weeks) ]
  Overall survival is defined as the time from the date of start of study treatment until death due to any cause. Any participant not died at the time of analysis was censored based on the last recorded date on which the participant was known to be alive. The OS was estimated using Kaplan-Meier method.

Original Primary Outcome Measures (submitted: November 13, 2014)

• Number of subjects with adverse events in each dose level (Part A) [ Time Frame: 2 years ]
  Number of subjects with adverse events in each dose level
• Number of subjects with progression free survival (Part B) [ Time Frame: 2 years ]
  Number of subjects with progression free survival
• Number of subjects with adverse event in combination dose (Part B) [ Time Frame: 2 years ]
  Number of subjects with adverse event in combination dose

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of ADXS11-001 or MEDI4736 Alone or Combination In Cervical or Human Papillomavirus (HPV)+ Head & Neck Cancer
• Official Title: 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
• 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Cervical Cancer
• Cancer
• Head and Neck Cancer

Intervention

• Drug: ADXS11-001
• Drug: MEDI4736

Study Arms

• Experimental: 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.
  Interventions:

  • Drug: ADXS11-001
  • Drug: MEDI4736
• Experimental: 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.
  Interventions:

  • Drug: ADXS11-001
  • Drug: MEDI4736
• Experimental: 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.
  Interventions:

  • Drug: ADXS11-001
  • Drug: MEDI4736
• Experimental: 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.
  Intervention: Drug: MEDI4736
• Experimental: 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.
  Interventions:

  • Drug: ADXS11-001
  • Drug: MEDI4736

• Publications *: 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: February 20, 2023): 75
• Original Estimated Enrollment (submitted: November 13, 2014): 66
• Actual Study Completion Date: November 20, 2020
• Actual Primary Completion Date: July 9, 2019 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02291055
• Other Study ID Numbers: ADXS001-04
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Advaxis, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Advaxis, Inc.
• Original Study Sponsor: Same as current
• Collaborators: MedImmune LLC
• Investigators: Not Provided
• PRS Account: Advaxis, Inc.
• Verification Date: February 2023