A Phase 1/2, Open-label Study to Evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination With Durvalumab Versus Nivolumab Monotherapy in Subjects With Select Advanced Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 97
- 试验地点
- 28
- 主要终点
- Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase
研究概览
简要总结
To evaluate the Safety and Antitumor Activity of MEDI0680 (AMP-514) in Combination with Durvalumab versus Nivolumab Monotherapy in Participants with Select Advanced Malignancies.
详细描述
This is a multicenter, open-label, Phase 1/2 study to evaluate the safety, tolerability, PK, immunogenicity, and antitumor activity of MEDI0680 in combination with durvalumab or nivolumab monotherapy in adult immunotherapy-naïve participants with selected advanced malignancies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Must be 18 years or older
- •Eastern Cooperative Oncology Group performance status of 0-1
- •Adequate organ function
- •At least 1 prior line of therapy
排除标准
- •Concurrent enrollment in another clinical study, unless in follow-up period or it is an observational study
- •Concurrent chemotherapy, immunotherapy, biologic, or hormonal therapy for cancer treatment
- •Prior treatment with immunotherapy
结局指标
主要结局
Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAES in Dose-escalation Phase
时间窗: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of participants in dose-escalation phase with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs is defined as any abnormal finding in the vital sign parameters (blood pressure, heart rate, body temperature, and respiratory rate). Abnormal physical examination findings are defined as any abnormal finding in the following body systems: head and neck, respiratory, cardiovascular, gastrointestinal, urogenital, musculoskeletal, neurological, psychiatric, dermatological, hematologic/lymphatic, and endocrine systems, and weight.
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs in Dose-escalation Phase
时间窗: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of participants in dose-escalation phase with abnormal ECG parameters reported as TEAEs are reported.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-escalation Phase
时间窗: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
Number of participants in dose-escalation phase with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters are defined as any abnormal finding during analysis of serum chemistry, hematology, coagulation, and urine.
Objective Response Rate (ORR) Based on Investigator-assessed Response Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) in Dose-expansion Phase
时间窗: From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months)
The ORR is defined as best overall response of confirmed complete response (CR) or confirmed partial response (PR) based on RECIST v1.1. The CR is defined as disappearance of all target and non-target lesions and no new lesions. The PR is defined as \>= 30% decrease in the sum of 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 in-between.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) in Dose-escalation Phase
时间窗: Day 1 through 90 days post end of treatment (approximately 5 years 10 months)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An 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.
次要结局
- Disease Control Rate (DCR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase(From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months))
- Progression Free Survival (PFS) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase(From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months))
- Duration of Response (DoR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase(From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months))
- TTR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase(From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant))
- Time to Response (TTR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase(From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months))
- BOR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase(From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant))
- ORR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase(From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant))
- DCR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase(From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant))
- Best Overall Response (BOR) Based on Investigator-assessed RECIST v1.1 in Dose-expansion Phase(From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months))
- Overall Survival in Dose-expansion Phase(From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months))
- PFS Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase(From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant))
- OS in Dose-escalation Phase(From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant))
- Serum Concentration of MEDI0680 in Dose-escalation and Dose-expansion Phases(Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1)
- ORR for Participants With Programmed Cell Death Ligand 1 (PD-L1) Status Positive and Negative in Dose-expansion Phase(From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months))
- DoR Based on Investigator-assessed Modified RECIST v1.1 in Dose-escalation Phase(From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant))
- Number of Participants With TEAEs and TESAEs in Dose-expansion Phase(Day 1 through 90 days post end of treatment (approximately 5 years 10 months))
- Serum Concentration of Durvalumab in Dose-escalation and Dose-expansion Phases(Pre-dose and end of infusion on Cycle 1 Day 1, Cycle 1 Day 15, and Cycle 2 Day 1)
- Number of Participants With Abnormal ECGs Reported as TEAEs in Dose-expansion Phase(Day 1 through 90 days post end of treatment (approximately 5 years 10 months))
- Percent Change From Baseline in Tumor Size in Dose-escalation Phase (Based on Investigator-assessed Modified RECIST v1.1) and Dose-expansion Phase (Based on Investigator-assessed RECIST v1.1)(From baseline (Day -42 to Day -1) through disease progression or EOT (approximately 12 months for each participant for dose-escalation phase and approximately 5 years 10 months for dose-expansion phase))
- Number of Participants With Positive Anti-drug Antibodies (ADA) to MEDI0680 in Dose-escalation and Dose-expansion Phases(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months))
- Number of Participants With Positive ADA to Durvalumab in Dose-escalation and Dose-expansion Phases(Cycle 1 Day 1, Cycle 2 Day 1, Cycle 5 Day 1, Cycle 8 Day 1, Cycle 11 Day 1, 90 and 180 days post end of treatment (approximately 5 years and 10 months))
- Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs in Dose-expansion Phase(Day 1 through 90 days post end of treatment (approximately 5 years 10 months))
- Number of Participants With Abnormal Vital Signs and Physical Examinations Reported as TEAEs in Dose-expansion Phase(Day 1 through 90 days post end of treatment (approximately 5 years 10 months))
- Antitumor Activity of MEDI0680 and Durvalumab Versus Nivolumab Monotherapy in Immunotherapy-Naïve Participants With Advanced or Metastatic Clear-cell Renal Cell Carcinoma (ccRCC) Based on Blinded Independent Central Review (BICR) in Dose-expansion Phase(From baseline (Day -42 to Day -1) through disease progression or end of treatment (approximately 5 years 10 months))