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

Status

Terminated

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02291055

Enrollment

Registered

2014-11-14

Start date

2015-04-30

Completion date

2020-11-20

Last updated

2023-03-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cervical Cancer, Cancer, Head and 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.

Interventions

DRUGADXS11-001

DRUGMEDI4736

Study design

Allocation

RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B	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	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	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	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	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	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	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	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	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	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	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	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	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.

Countries

United States

Participant flow

Recruitment details

Participants were enrolled at study centers in the United States.

Pre-assignment details

Participants with a diagnosis of cervical cancer and human papillomavirus (HPV) positive squamous cell carcinoma of head and neck (SCCHN) were enrolled in the study.

Participants by arm

Arm	Count
Part A Escalation (Cervical): 1×10^9 CFU ADXS11-001/ 3 mg/kg MEDI4736 Participants with cervical cancer received MEDI4736 3 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.	5
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.	5
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.	11
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.	27
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.	27
Total	75

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Death	2	2	5	8	12
Overall Study	Lost to Follow-up	0	0	0	1	2
Overall Study	Other	0	2	1	4	0
Overall Study	Progressive Disease	0	0	1	4	2
Overall Study	Study Terminated by Sponsor	0	0	0	5	1
Overall Study	Withdrawal by Subject	3	1	1	5	10

Baseline characteristics

Characteristic	Part A Escalation (Cervical): 1×10^9 CFU ADXS11-001/ 3 mg/kg MEDI4736	Part A Escalation (Cervical and Head and Neck): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736	Part A Expansion (Head and Neck): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736	Part B Expansion (Cervical): 10 mg/kg MEDI4736	Part B Expansion (Cervical): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736	Total
Age, Categorical <=18 years	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Age, Categorical >=65 years	0 Participants	1 Participants	2 Participants	4 Participants	0 Participants	7 Participants
Age, Categorical Between 18 and 65 years	5 Participants	4 Participants	9 Participants	23 Participants	27 Participants	68 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	1 Participants	2 Participants	3 Participants	6 Participants	12 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants	4 Participants	9 Participants	24 Participants	21 Participants	63 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Race/Ethnicity, Customized Race Asian	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	2 Participants
Race/Ethnicity, Customized Race Black or African American	1 Participants	0 Participants	1 Participants	5 Participants	3 Participants	10 Participants
Race/Ethnicity, Customized Race Other	0 Participants	1 Participants	0 Participants	3 Participants	2 Participants	6 Participants
Race/Ethnicity, Customized Race White	3 Participants	4 Participants	10 Participants	19 Participants	21 Participants	57 Participants
Sex: Female, Male Female	5 Participants	4 Participants	0 Participants	27 Participants	27 Participants	63 Participants
Sex: Female, Male Male	0 Participants	1 Participants	11 Participants	0 Participants	0 Participants	12 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	2 / 5	2 / 5	7 / 11	8 / 27	12 / 27
other Total, other adverse events	5 / 5	5 / 5	11 / 11	25 / 27	27 / 27
serious Total, serious adverse events	2 / 5	3 / 5	4 / 11	13 / 27	15 / 27

Outcome results

Primary

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B

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.

Time frame: From first dose until 30 days after last dose (maximum duration: 98 weeks)

Population: All Treated Population.

Arm	Measure	Group	Value (NUMBER)
Part A Escalation (Cervical): 1×10^9 CFU ADXS11-001/ 3 mg/kg MEDI4736	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B	TEAEs	5 participants
Part A Escalation (Cervical): 1×10^9 CFU ADXS11-001/ 3 mg/kg MEDI4736	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B	TESAEs	2 participants
Part A Escalation (Cervical and Head and Neck): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B	TEAEs	5 participants
Part A Escalation (Cervical and Head and Neck): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B	TESAEs	3 participants
Part A Expansion (Head and Neck): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B	TEAEs	11 participants
Part A Expansion (Head and Neck): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B	TESAEs	4 participants
Part B Expansion (Cervical): 10 mg/kg MEDI4736	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B	TESAEs	13 participants
Part B Expansion (Cervical): 10 mg/kg MEDI4736	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B	TEAEs	25 participants
Part B Expansion (Cervical): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B	TEAEs	27 participants
Part B Expansion (Cervical): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) in Part A and Part B	TESAEs	15 participants

Primary

Overall Survival: Cervical Cancer Population

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.

Time frame: From first dose until death (maximum duration: 146 weeks)

Population: All Treated Population.

Arm	Measure	Value (MEDIAN)
Part A Escalation (Cervical): 1×10^9 CFU ADXS11-001/ 3 mg/kg MEDI4736	Overall Survival: Cervical Cancer Population	NA months
Part A Escalation (Cervical and Head and Neck): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736	Overall Survival: Cervical Cancer Population	9.3 months
Part A Expansion (Head and Neck): 1×10^9 CFU ADXS11-001/ 10 mg/kg MEDI4736	Overall Survival: Cervical Cancer Population	9.2 months

Primary

Overall Survival: HPV+ Head and Neck Cancer Population

Time frame: From first dose until death (maximum duration: 146 weeks)

Population: All Treated Population.

Arm	Measure	Value (MEDIAN)
Part A Escalation (Cervical): 1×10^9 CFU ADXS11-001/ 3 mg/kg MEDI4736	Overall Survival: HPV+ Head and Neck Cancer Population	4.8 months

Primary

Percentage of Participants With Disease Control as Per irRECIST Criteria (Part A and Part B): Cervical Cancer Population

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.