A Phase 1/2 Study of HDAC Inhibitor, Mocetinostat, in Combination With PD-L1 Inhibitor, Durvalumab, in Advanced or Metastatic Solid Tumors and Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 83
- 试验地点
- 15
- 主要终点
- Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During the First 28-day Cycle of Combination Treatment In Phase 1
研究概览
简要总结
Mocetinostat (MGCD0103) is an orally administered HDAC inhibitor. Durvalumab (MEDI4736) is a human monoclonal antibody that is an inhibitor of the Programmed Cell Death Ligand (or PD-L1). Durvalumab is also known as a checkpoint inhibitor.
This study is evaluating the combination regimen of mocetinostat and durvalumab in participants with Advanced or Metastatic Solid Tumors and Non-Small Cell Lung Cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Phase 1-Diagnosis of advanced or metastatic solid tumor; Phase 2-Diagnosis of NSCLC
- •Not amenable to treatment with curative intent
- •Adequate bone marrow and organ function
排除标准
- •Impaired heart function
- •Uncontrolled tumor in the brain
- •Other active cancer
研究组 & 干预措施
Phase 1: Dose Escalation - 50 mg
The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase.
干预措施: Mocetinostat - 50 mg (Drug)
Phase 1: Dose Escalation - 50 mg
The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase.
干预措施: Durvalumab - 1500 mg (Drug)
Phase 1: Dose Escalation - 70 mg
The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase.
干预措施: Mocetinostat - 70 mg (Drug)
Phase 1: Dose Escalation - 70 mg
The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase.
干预措施: Durvalumab - 1500 mg (Drug)
Phase 1: Dose Escalation - 90 mg
The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase.
干预措施: Mocetinostat - 90 mg (Drug)
Phase 1: Dose Escalation - 90 mg
The Phase 1 dose escalation established the recommended phase 2 dose (RP2D) of mocetinostat. Participants with advanced solid tumors were included in this Phase.
干预措施: Durvalumab - 1500 mg (Drug)
Phase 2: Combination Regimen - Cohort 1
Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort.
干预措施: Mocetinostat - Recommended Phase 2 Dose (70 mg) (Drug)
Phase 2: Combination Regimen - Cohort 1
Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with no/low programmed cell death ligand 1 (PD-L1) expression were included in this cohort.
干预措施: Durvalumab - 1500 mg (Drug)
Phase 2: Combination Regimen - Cohort 2
Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort.
干预措施: Mocetinostat - Recommended Phase 2 Dose (70 mg) (Drug)
Phase 2: Combination Regimen - Cohort 2
Participants with non-small cell lung cancer (NSCLC) who were naïve to treatment with immunotherapy, and had a tumor with high programmed cell death ligand 1 (PD-L1) expression were included in this cohort.
干预措施: Durvalumab - 1500 mg (Drug)
Phase 2: Combination Regimen - Cohort 3
Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort.
干预措施: Mocetinostat - Recommended Phase 2 Dose (70 mg) (Drug)
Phase 2: Combination Regimen - Cohort 3
Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent with clinical benefit response followed by progression of disease were included in this cohort.
干预措施: Durvalumab - 1500 mg (Drug)
Phase 2: Combination Regimen - Cohort 4
Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort.
干预措施: Mocetinostat - Recommended Phase 2 Dose (70 mg) (Drug)
Phase 2: Combination Regimen - Cohort 4
Participants with non-small cell lung cancer (NSCLC) who have been previously treated with an anti-programmed cell death ligand 1 (PD-L1) or anti-programmed cell death 1 (PD-1) agent who had progression of disease ≤ 16 weeks after initiation of treatment were included in this cohort.
干预措施: Durvalumab - 1500 mg (Drug)
结局指标
主要结局
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) During the First 28-day Cycle of Combination Treatment In Phase 1
时间窗: 28 days
Toxicities were graded using the National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) version 4.03. Any of the following events considered to be causally related to treatment with mocetinostat in combination with durvalumab that occurred during Phase 1 were considered a DLT: * Any Grade 4 immune-related adverse event (irAE) * Grade 3 or greater colitis * Grade 3 or greater noninfectious pneumonitis * Grade 2 pneumonitis that did not resolve to ≤ Grade 1 within 3 days of the initiation of maximal supportive care * Grade 3 irAE (excluding colitis or pneumonitis) that: * Did not resolve to Grade 2 within 3 days after onset of the event despite optimal medical management including systemic corticosteroids, or * Did not resolve to Grade ≤1 or Baseline within 14 days * Liver transaminase elevation \>8×upper limit of normal (ULN) or total bilirubin \>5×ULN * Grade 3 or greater non-irAE, except nausea, vomiting, anorexia, dehydration, or diarrhea
Objective Response Rate (ORR)
时间窗: Up to approximately 10 months
Objective Response Rate (ORR) was defined as the number of participants documented to have a confirmed Complete Response (CR) or Partial Response (PR). Complete Response was defined as the complete disappearance of all target lesions with the exception of nodal disease. Partial Response was defined at least a 30% decrease in the sum of diameters of target measurable lesions. Responses were determined by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Participants without response data were counted as non-responders. Inferential statistical analyses were conducted for Phase 2 only, as efficacy was not part of the Phase 1 objectives.
次要结局
- Number of Participants Experiencing Treatment-Emergent Adverse Events(Day 1 to 28 days after last dose of study treatment (up to a maximum of 125 weeks in phase 1 and a maximum of 92 weeks in phase 2))
- 1-Year Survival Rate(1 year)
- Concentration of Durvalumab in Blood Plasma(Cycle 1 Day 1 pre-dose + end of infusion, Cycle 1 Day 15 pre-mocetinostat dose, Cycle 2 Day 1 pre-dose, Cycle 3 Day 1 pre-dose, Cycle 4 Day 1 pre-dose + end of infusion, Cycle 7 Day 1 pre-dose + 90 days after participant's last dose (Up to max 133 weeks))
- Clinical Benefit Rate (CBR)(Up to approximately 10 months)
- Progression-Free Survival (PFS)(Randomization until progressive disease or death due to any cause (up to 42 months))
- Overall Survival (OS)(From date of first study treatment until death due to any cause (up to 42 months))
- Number of Participants With Tumor Expression of Programmed Cell Death Ligand 1 (PD-L1) at Baseline(Baseline)
- Duration of Response (DR)(Up to approximately 10 months)
- Concentration of Mocetinistat in Blood Plasma(Cycle 1 Day 1 pre-dose, 1, 3, and 7 hours post-dose, Cycle 1 Day 15 pre-dose and 1 hour post-dose, Cycle 2 Day 1 pre-dose and 1 hour post-dose, Cycle 3 Day 1 pre-dose and 1 hour post-dose and Cycle 7 Day 1 pre-dose (each cycle is 28 days))
- Number of Participants With the Presence of Anti-Drug Antibody (ADA) in the Blood(Up to approximately 10 months)