Phase 2
N=35
Safety and Efficacy of MEDI0457 and Durvalumab in Participants With Human Papilloma Virus (HPV) Associated Recurrent/Metastatic Head and Neck Cancer
Head and Neck Cancer · Human Papilloma Virus
Bottom Line
View on ClinicalTrials.gov: NCT03162224 ↗Enrolled (actual)
35
Serious AEs
40.0%
Results posted
Aug 2022
Primary outcome: Primary: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) — 15; 9; 11; 4 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- MEDI0457 (Drug); CELLECTRA®5P device (Device); Durvalumab (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- MedImmune LLC
- Primary completion
- Mar 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) |
15; 9; 11; 4; 4; 6 | — |
| PRIMARY Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs |
2; 1; 3; 1; 1; 3 | — |
| PRIMARY Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs |
1; 2; 1; 0; 0; 3 | — |
| PRIMARY Number of Participants With Abnormal Vital Signs and/or Physical Examination Reported as TEAEs |
1; 4; 2; 4; 2; 2 | — |
| PRIMARY Number of Participants Who Received Any Concomitant Medications During the Study |
15; 9; 11 | — |
| PRIMARY Number of Participants With Shift >=3 Changed From Baseline in Eastern Cooperative Oncology Group Performance (ECOG) Status |
0; 0; 1 | — |
| PRIMARY Percentage of Participants With Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in Response-evaluable Population |
33.3; 28.6; 20.0 | — |
| SECONDARY Percentage of Participants With Objective Response by RECIST Version 1.1 in As-treated Population |
33.3; 22.2; 18.2 | — |
| SECONDARY Percentage of Participants With Objective Response by Immune-related RECIST (irRECIST) in Response-evaluable Population |
41.7; 28.6; 20.0 | — |
| SECONDARY Percentage of Participants With Objective Response by irRECIST in As-treated Population |
40.0; 22.2; 18.2 | — |
| SECONDARY Disease Control Rate (DCR) at Week 16 by RECIST Version 1.1 in Response-evaluable Population |
50.0; 28.6; 50.0 | — |
| SECONDARY DCR at Week 16 by RECIST Version 1.1 in As-treated Population |
53.3; 33.3; 45.5 | — |
| SECONDARY Progression Free Survival (PFS) |
9.5; 2.3; 3.8 | — |
| SECONDARY Overall Survival (OS) |
NA; 29.2; 19.2 | — |
| SECONDARY Number of Participants With Positive Anti-Drug Antibodies (ADA) to Durvalumab |
0; 0; 1; 0; 0; 0 | — |
| SECONDARY Serum Concentrations of Durvalumab |
0.767; 1.505; 92.163; 89.094; 94.665; 190.061 | — |
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
- Male and female participants 18 years and older
- 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.
- Recurrent or metastatic disease that has been treated with at least one platinum-containing regimen and lacking a curative treatment option.
- 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
- Any concurrent chemotherapy, immune-mediated therapy or biologic or hormonal therapy for cancer treatment Active or prior documented autoimmune disease with some exceptions.
- 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.
- 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).
Data sourced from ClinicalTrials.gov (NCT03162224). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.