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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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).
排除标准
- 未提供
研究组 & 干预措施
First-line Recurrent/Metastatic (1L R/M) Platinum Non-refractory
Participants with recurrent or metastatic disease and were non-refractory to neoadjuvant/adjuvant platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then every 8 weeks (Q8W) and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then every 4 weeks (Q4W) until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.
干预措施: MEDI0457 (Drug)
First-line Recurrent/Metastatic (1L R/M) Platinum Non-refractory
Participants with recurrent or metastatic disease and were non-refractory to neoadjuvant/adjuvant platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then every 8 weeks (Q8W) and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then every 4 weeks (Q4W) until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.
干预措施: CELLECTRA®5P device (Device)
First-line Recurrent/Metastatic (1L R/M) Platinum Non-refractory
Participants with recurrent or metastatic disease and were non-refractory to neoadjuvant/adjuvant platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then every 8 weeks (Q8W) and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then every 4 weeks (Q4W) until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.
干预措施: Durvalumab (Drug)
1L R/M Platinum Refractory
Participants with R/M disease and were refractory to neoadjuvant/adjuvant platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then Q8W and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then Q4W until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.
干预措施: MEDI0457 (Drug)
1L R/M Platinum Refractory
Participants with R/M disease and were refractory to neoadjuvant/adjuvant platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then Q8W and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then Q4W until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.
干预措施: CELLECTRA®5P device (Device)
1L R/M Platinum Refractory
Participants with R/M disease and were refractory to neoadjuvant/adjuvant platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then Q8W and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then Q4W until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.
干预措施: Durvalumab (Drug)
Second-line (2L) + R/M
Participants with R/M disease and were treated with 1 or more lines of platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then Q8W and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then Q4W until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.
干预措施: MEDI0457 (Drug)
Second-line (2L) + R/M
Participants with R/M disease and were treated with 1 or more lines of platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then Q8W and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then Q4W until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.
干预措施: CELLECTRA®5P device (Device)
Second-line (2L) + R/M
Participants with R/M disease and were treated with 1 or more lines of platinum based chemotherapy, will receive MEDI0457 7 mg intramuscularly followed by electroporation on Day 1 of Weeks 1, 3, 7, 12, and then Q8W and durvalumab 1500 mg intravenously on Day 1 of Week 4 and then Q4W until disease progression, unacceptable toxicity, or withdrawal of consent, whichever occurs first.
干预措施: Durvalumab (Drug)
结局指标
主要结局
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
时间窗: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. There will be no updated results for this outcome measures at the time of end of study.
Number of Participants With Abnormal Laboratory Parameters Reported as TEAEs
时间窗: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Any laboratory abnormality during analysis of hematology, clinical chemistry, thyroid function tests, and urinalysis that was new in onset or worsened in severity or frequency from the baseline condition and required therapeutic intervention or diagnostic tests, led to discontinuation of study treatment, had accompanying or inducing symptoms or signs, or judged by the Investigator as clinically significant was recorded as AE. Participants with abnormal laboratory parameters reported as TEAEs are reported.
Number of Participants With Abnormal Electrocardiogram (ECG) Reported as TEAEs
时间窗: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Participants with ECG abnormalities reported as TEAEs are reported.
Number of Participants Who Received Any Concomitant Medications During the Study
时间窗: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Participants who received concomitant medications which were ongoing at the start of treatment or started after the study treatment are included.
Number of Participants With Abnormal Vital Signs and/or Physical Examination Reported as TEAEs
时间窗: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Vital sign assessment included body temperature, respiration rate, pulse oximetry, blood pressure, heart rate, and weight. Participants with abnormal vital sign and/or abnormal physical examination reported as TEAEs are reported.
Number of Participants With Shift >=3 Changed From Baseline in Eastern Cooperative Oncology Group Performance (ECOG) Status
时间窗: Day 1 through 90 days after the last dose of study drug (approximately 45 months)
Participants with shift \>=3 changed from baseline in ECOG status are reported. ECOG performance status is used by doctors and researchers to assess how a participant's disease is progressing, assess how the disease affects the daily living activities of the participant and determine appropriate treatment and prognosis. The scores are: 0 = Fully Active, able to carry out all pre-disease performance without restrictions; 1 = Restricted activity but ambulatory and able to carry out light work or work of a sedentary nature; 2 = Ambulatory and capable of self-care but unable to carry out work activities; 3 = Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely Disabled, unable to carry out any self-care and totally confined to bed or chair; 5 = Dead.
Percentage of Participants With Objective Response by Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 in Response-evaluable Population
时间窗: Day 1 through end of study (approximately 45 months)
The objective response is defined as confirmed complete response (CR) or confirmed partial response (PR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) guidelines. The CR is defined as disappearance of all target and non-target lesions, no new lesions, and normalization of tumor marker level. The PR is defined as \>= 30% decrease in the sum of the diameters of target lesions compared to baseline and no new non-target lesion. A confirmed CR or PR is defined as 2 CRs or 2 PRs that were separated by at least 4 weeks with no evidence of progression or not evaluable response in-between. Percentage of participants with objective response is reported.
次要结局
- DCR at Week 16 by RECIST Version 1.1 in As-treated Population(Week 16)
- Serum Concentrations of Durvalumab(Pre-dose (up to 60 minutes prior to durvalumab administration) on Week 4, Week 8, and Week 16)
- Progression Free Survival (PFS)(Day 1 through end of study (approximately 45 months))
- Overall Survival (OS)(Day 1 through end of study (approximately 45 months))
- Percentage of Participants With Objective Response by RECIST Version 1.1 in As-treated Population(Day 1 through end of study (approximately 45 months))
- Percentage of Participants With Objective Response by Immune-related RECIST (irRECIST) in Response-evaluable Population(Day 1 through end of study (approximately 45 months))
- Percentage of Participants With Objective Response by irRECIST in As-treated Population(Day 1 through end of study (approximately 45 months))
- Disease Control Rate (DCR) at Week 16 by RECIST Version 1.1 in Response-evaluable Population(Week 16)
- Number of Participants With Positive Anti-Drug Antibodies (ADA) to Durvalumab(Pre-dose (up to 60 minutes prior to durvalumab administration) on Week 4, Week 8, and Week 16)