Clinical trial NCT03162224: Safety and Efficacy of MEDI0457 and Durvalumab in Participants With Human Papilloma Virus (HPV) Associated Recurrent/Metastatic Head and Neck Cancer
Official title: A Phase 1b/2a, Multi-Center Open-Label Study to Evaluate the Safety and Efficacy of Combination Treatment With MEDI0457 (INO-3112) and Durvalumab (MEDI4736) in Patients With Recurrent/Metastatic HPV Associated Head and Neck Squamous Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Head and Neck Cancer
Human Papilloma Virus
Keywords: Head and Neck Squamous Cell Carcinoma
Oropharyngeal Cancer
HPV
Human Papilloma Virus
Cancer Immunotherapy
Check point inhibitors
PD-L1 inhibitor
Recurrent or Metastatic Cancer
Durvalumab
MEDI0457
Antineoplastic agents
Neoplasms
Lead sponsor: MedImmune LLC
Sponsor class: INDUSTRY
First posted: 2017-05-22
Enrollment: 35
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a Phase 1b/2a, open-label, multi-center study to evaluate the safety and tolerability, anti-tumor activity, and immunogenicity of MEDI0457 (also known as INO 3112) a HPV Deoxyribonucleic Acid (DNA) vaccine in combination with durvalumab (also known as MEDI4736) which is a human monoclonal antibody directed against Programmed Death Ligand 1 (PD-L1), which blocks the interaction of PD-L1 with PD-1 and Cluster of differentiation 80 (CD80).

An initial three to 12 participants (Safety Analysis Run-in participants) will be enrolled and assessed for safety before additional participants are enrolled.

The initial safety analysis run-in participants along with an approximate total of 50 participants with human papilloma virus associated recurrent or metastatic head and neck squamous cell cancer (HNSCC) will be enrolled in this study and evaluated also for anti-tumor efficacy to MEDI0457 in combination with durvalumab.


Eligibility criteria: Inclusion Criteria:

1. Male and female participants 18 years and older
2. Histologically or cytologically confirmed diagnosis of HNSCC associated with HPV by a p16 immunohistochemistry (IHC) assay or HPV-16 or HPV-18 positive by nucleic acid testing.
3. Recurrent or metastatic disease that has been treated with at least one platinum-containing regimen and lacking a curative treatment option.
4. Participants who are platinum ineligible may be enrolled if they have received and failed an approved treatment and lack a treatment option with curative potential.

Exclusion criteria:

1. Any concurrent chemotherapy, immune-mediated therapy or biologic or hormonal therapy for cancer treatment Active or prior documented autoimmune disease with some exceptions.
2. Current or prior use of immunosuppressive medication within 14 days prior to first study dose, with the exception of intranasal and inhaled corticosteroids or systemic corticosteroids at doses not to exceed 10 mg/day of prednisone or equivalent. Steroids as premedication for hypersensitivity reactions due to radiographic contrast agents are allowed.
3. No prior exposure to immune-mediated therapy defined as prior exposure to T-cell and natural killer cell directed therapy (e.g., anti-PD-1, anti-PD-L1, anti-CD137, and anti-CTLA4, etc).

Primary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
timeFrame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
measure: Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs
timeFrame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
measure: Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs
timeFrame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
measure: Number of Participants With Abnormal Vital Signs and/or Physical Examination Reported as TEAEs
timeFrame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
measure: Number of Participants Who Received Any Concomitant Medications During the Study
timeFrame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
measure: Number of Participants With Shift >=3 Changed From Baseline in Eastern Cooperative Oncology Group Performance (ECOG) Status
timeFrame: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
measure: Percentage of Participants With Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in Response-evaluable Population
timeFrame: Day 1 through end of study (approximately 45 months)
Secondary outcomes:
measure: Percentage of Participants With Objective Response by RECIST Version 1.1 in As-treated Population
timeFrame: Day 1 through end of study (approximately 45 months)
measure: Percentage of Participants With Objective Response by Immune-related RECIST (irRECIST) in Response-evaluable Population
timeFrame: Day 1 through end of study (approximately 45 months)
measure: Percentage of Participants With Objective Response by irRECIST in As-treated Population
timeFrame: Day 1 through end of study (approximately 45 months)
measure: Disease Control Rate (DCR) at Week 16 by RECIST Version 1.1 in Response-evaluable Population
timeFrame: Week 16
measure: DCR at Week 16 by RECIST Version 1.1 in As-treated Population
timeFrame: Week 16
measure: Progression Free Survival (PFS)
timeFrame: Day 1 through end of study (approximately 45 months)
measure: Overall Survival (OS)
timeFrame: Day 1 through end of study (approximately 45 months)
measure: Number of Participants With Positive Anti-Drug Antibodies (ADA) to Durvalumab
timeFrame: Pre-dose (up to 60 minutes prior to durvalumab administration) on Week 4, Week 8, and Week 16
measure: Serum Concentrations of Durvalumab
timeFrame: Pre-dose (up to 60 minutes prior to durvalumab administration) on Week 4, Week 8, and Week 16
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: Research Site
state: California
city: Orlando
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Detroit
country: United States
facility: Research Site
state: Michigan
city: Minneapolis
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Morristown
country: United States
facility: Research Site
state: New Jersey
city: Bronx
country: United States
facility: Research Site
state: New York
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
Study officials:
affiliation: Study Director
name: MedImmune LLC
role: STUDY_DIRECTOR
References: