A PHASE 1 STUDY OF PF-05082566 AS A SINGLE AGENT IN PATIENTS WITH ADVANCED CANCER, AND IN COMBINATION WITH RITUXIMAB IN PATIENTS WITH NON-HODGKIN'S LYMPHOMA (NHL)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 190
- 试验地点
- 39
- 主要终点
- Number of Participants With DLTs in First 2 Cycles of Portion B
研究概览
简要总结
A study of PF-05082566, a 4-1BB agonist monoclonal antibody (mAb), in patients with solid tumors or b-cell lymphomas, and in combination with rituximab in patients with CD20 positive Non-Hodgkin's Lymphoma (NHL).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Portion A
PF-05082566 single agent in patients with advanced cancer
干预措施: PF-05082566 (Drug)
Portion B
PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
干预措施: rituximab (Drug)
Portion B
PF-05082566 in combination with rituximab in patients with Non-Hodgkin's Lymphoma
干预措施: PF-05082566 (Drug)
结局指标
主要结局
Number of Participants With DLTs in First 2 Cycles of Portion B
时间窗: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion B (up to 57 days, each cycle = 28 days)
DLT: Any of the following AEs occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 in combination with rituximab for Portion B and not related to progressive disease. Hematologic: Grade 4 neutropenia lasting more than (\>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis. Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT). Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). Each cycle=28 days.
Number of Participants With Dose-Limiting Toxicities (DLTs) in First 2 Cycles of Portion A
时间窗: Cycle 1 Day 1 to Cycle 2 Day 29 in Portion A (up to 57 days, each cycle = 28 days)
DLT: Any of the following adverse events (AEs) occurred in the first 2 cycles of treatment (up to 28 days post second dose) which was attributed to PF-05082566 alone for Portion A and not related to progressive disease. Hematologic: Grade 4 neutropenia lasting more than (\>)7 days; febrile neutropenia; neutropenic infection; Grade ≥3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; Grade ≥3 hemolysis. Non-Hematologic: Grade ≥3 toxicities, except those Grade 3 events that responded to treatment (eg, Grade 3 nausea, vomiting, diarrhea responding to standard medical supportive care within 48 hours would not be considered a DLT). Severity of AEs were graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 (Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE). Each cycle=28 days.
次要结局
- Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A(Up to approximately 2 years)
- Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion A(Up to approximately 2 years)
- PF-05082566 Pre-dose Trough Concentration During Multiple Dosing (Ctrough) in Portion A(Day 1 pre-dose of Cycle 2)
- PF-05082566 AUC From Time 0 to Time of Dosing Interval (AUCtau) in Portion A(Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.)
- Percentage of Participants Achieving Objective Response Per Response Evaluation Criteria in Solid Tumor (RECIST) Version 1.1 in Portion A(Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years))
- PF-05082566 Maximum Observed Serum Concentration (Cmax) in Portion A(Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose)
- PF-05082566 Area Under the Serum Concentration-Time Profile (AUC) From Time 0 to the Time of the Last Measurable Concentration (AUClast) in Portion A(Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.)
- Overall Survival in Portion A(Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years))
- Number of Participants With Hematology Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B(Up to approximately 2 years)
- PF-05082566 Tmax in Portion B(Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.)
- Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) in Portion A(Up to approximately 2 years)
- Number of Participants With Treatment-Emergent AEs by Maximum National Cancer Institute Common Terminology Criteria for Adverse Event (NCI CTCAE) Grade in Portion A(Up to approximately 2 years)
- Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion A(Up to approximately 2 years)
- PF-05082566 Clearance (CL) in Portion A(Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.)
- PF-05082566 Volume of Distribution at Steady State (Vss) in Portion A(Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.)
- Number of Participants With Positive Anti-Drug Antibody (ADA) for PF-05082566 in Portion A(Up to approximately 2 years)
- Progression-Free Survival in Portion A(Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years))
- PF-05082566 Cmax in Portion B(Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.)
- PF-05082566 Time for Maximum Observed Serum Concentration (Tmax) in Portion A(Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.)
- PF-05082566 AUC From Time 0 to Infinity (AUCinf) in Portion A(Day 1 of Cycle 1 and Cycle 2 at pre-dose, and 1, 1.5, 2, 6, 24, 48, 168, 336 and 504 hours post-dose.)
- Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion A(Up to approximately 2 years)
- Number of Participants With Chemistries Laboratory Abnormalities by Maximum NCI CTCAE Grade in Portion B(Up to approximately 2 years)
- PF-05082566 AUCinf in Portion B(Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose.)
- Rituximab Cmax and Ctrough in Portion B(Day 1 pre-dose of Cycle 2)
- Number of Participants With Treatment-Emergent AEs by Maximum NCI CTCAE Grade in Portion B(Up to approximately 4 years)
- Number of Participants With Clinically Significant Vital Sign Abnormalities in Portion B(Up to approximately 2 years)
- PF-05082566 Ctrough in Portion B(Day 1 pre-dose of Cycle 2)
- PF-05082566 AUClast in Portion B(Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.)
- PF-05082566 Vss in Portion B(Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.)
- Number of Participants With QTc Interval Meeting Categorical Summarization Criteria in Portion B(Up to approximately 2 years)
- Percentage of Participants Achieving Objective Response Per Cheson 2007 Criteria in Portion B(Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years))
- Duration of Response in Portion A(Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years))
- Time to Response in Portion A(Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years))
- Number of Participants With Treatment-Emergent AEs and SAEs in Portion B(Up to approximately 4 years)
- Duration of Response in Portion B(Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years))
- PF-05082566 AUCtau in Portion B(Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.)
- PF-05082566 CL in Portion B(Cycle 1 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 144, 312, and 504 hours post-dose; Cycle 2 Day 1 pre-dose, 1.5, 2, 6, 24, 48, 168, 336, and 504 hours post-dose.)
- Number of Participants With Positive ADA for PF-05082566 and Rituximab in Portion B(Up to approximately 2 years)
- Progression-Free Survival in Portion B(Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years))
- Overall Survival in Portion B(Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years))
- Time to Response in Portion B(Every 8 weeks from Cycle 1 Day 1 for the first 10 months on study treatment, then every 16 weeks till follow-up visit (assessed up to approximately 2 years))