NCT02444793终止1 期
A PHASE 1B STUDY OF PF-05082566 IN COMBINATION WITH MOGAMULIZUMAB (KW-0761) IN PATIENTS WITH ADVANCED SOLID TUMORS
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 24
- 试验地点
- 20
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLT)
研究概览
简要总结
This study is a Phase 1b, open label, multi center, multi-dose trial designed to estimate the maximum tolerated dose (MTD) and select the recommended dose for phase 2 (RP2D) investigations of PF- 05082566 in combination with KW-0761 (mogamulizumab) in patients with advanced solid tumors. Once the MTD of PF-05082566 administered in combination with KW-0761 is estimated (dose finding), one or more expansion cohorts of patients with selected advanced solid tumors (dose-expansion ) will be enrolled to further characterize the combination in term of safety profile, anti tumor activity, pharmacokinetics, pharmacodynamics and biomarkers modulation.
研究设计
- 研究类型
- Interventional
- 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
- •Histological or cytological diagnosis of advanced/metastatic solid tumor malignancy. Dose Finding Cohorts: Tumor types will be limited to CRC, SCCHN, squamous NSCLC, bladder, or ovarian carcinomas which have progressed on standard therapy, or for which no standard therapy is available.
- •Measurable disease by RECIST version 1.
- •For Expansion Cohorts only: patients must have tumor accessible for biopsies (core needle biopsy or excision preferred).
- •Age 18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Adequate bone marrow, renal and liver function.
- •Serum/urine pregnancy test (for females of childbearing potential) negative at screening and before the patient will receive the study treatment.
- •Male and female patients of childbearing potential and at risk for pregnancy must agree to use two (2) highly effective methods of contraception throughout the study and for 60 days after the last dose of assigned study treatment.
排除标准
- •Active central nervous system primary or secondary malignancies, active seizure disorder, spinal cord compression, or carcinomatous meningitis.
- •Therapeutic or experimental monoclonal antibodies in last 60 days prior registration.
- •Systemic anticancer therapy or major surgery within 28 days prior to registration. In absence of toxicity from prior systemic anticancer therapy, 5 half-lives since completion of prior systemic anticancer therapy is allowed.
- •Systemic steroids, any other form of immunosuppressive therapy or radiation therapy within 14 days prior to registration.
- •Live vaccine within 30 days prior to registration.
- •Severe hypersensitivity reaction to treatment with another monoclonal antibody, known or suspected hypersensitivity to study drugs or any component of their formulation.
- •History of autoimmune disease or known inflammatory bowel disease.
- •Uncontrolled hypertension (blood pressure >150/100 mmHg despite optimal medical therapy) or any of the following within 12 months prior to registration: myocardial infarction, congenital long QT syndrome, torsade de points, arrhythmias, right bundle branch block and left anterior hemiblock uncontrolled angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, ongoing NCICTCAE Grade 2 cardiac dysrhythmias, atrial fibrillation or QTcF interval >470 msec.
研究组 & 干预措施
PF-05082566 + KW-0761
Experimental
During Parts 1 & 2 Mogamulizumab and PF-05082566 will be administered at appropriate intervals. Part 1: PF-05082566 dose escalation; increased doses of PF-05082566 IV are administered with mogamulizumab IV. Part 2: patients will be treated with the maximum tolerated dose established in Phase 1 for the combination.
干预措施: PF-05082566 (Drug)
PF-05082566 + KW-0761
Experimental
During Parts 1 & 2 Mogamulizumab and PF-05082566 will be administered at appropriate intervals. Part 1: PF-05082566 dose escalation; increased doses of PF-05082566 IV are administered with mogamulizumab IV. Part 2: patients will be treated with the maximum tolerated dose established in Phase 1 for the combination.
干预措施: KW-0761 (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLT)
时间窗: First 2 Cycles (28 days in each cycle)
DLTs was defined as any of the following adverse events (AEs) according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 at first 2 Cycles. Hematologic: (1) Grade 4 neutropenia lasting \>7 days; (2) Febrile neutropenia, defined as absolute neutrophil count (ANC) \<1000/mm3 with a single temperature of \>38.3 degrees C (101 degrees F) or a sustained temperature of \>=38 degrees C (100.4 degrees F) for more than 1 hour; (3) Grade \>=3 neutropenic infection; (4) Grade \>=3 thrombocytopenia with bleeding; (5) Grade 4 thrombocytopenia. Non-Hematologic: (1) Grade \>=3 non laboratory toxicities (excluding infusion reactions), except those that had not been maximally treated (eg, nausea, vomiting, diarrhea); (2) Grade \>=3 laboratory abnormalities (other than aspartate aminotransferase \[AST\]/alanine aminotransferase \[ALT\]) if: Medical intervention was required to treat the participant, or The abnormality led to hospitalization; (3) Grade 4 AST and ALT increase.
次要结局
- Number of Participants With Treatment-Emergent Adverse Events (All Causalities)(Day 1 up to 60 days after last dose of study treatment)
- Number of Participants With Treatment-Emergent Adverse Events (PF-05082566 Related)(Day 1 up to 60 days after last dose of study treatment)
- Number of Participants With Treatment-Emergent Adverse Events (Mogamulizumab Related)(Day 1 up tp 60 days after last dose of study treatment)
- Number of Participants With Hematology Laboratory Abnormalities as Characterized by Type, Frequency, Severity (as Graded by NCI CTCAE) -Grades 3 or 4(Screening (within 28 days prior to registration) up to 28 days (+7 days) after the last dose of study treatment)
- Number of Participants With Chemistries Laboratory Abnormalities as Characterized by Type, Frequency, Severity (as Graded by NCI CTCAE) -Grades 3 or 4(Screening (within 28 days prior to registration) up to 28 days (+7 days) after the last dose of study treatment)
- Number of Participants With Clinical Significant Observations in Vital Signs(Screening (within 28 days prior to registration) up to 28 days (+7 days) after the last dose of study treatment)
- Number of Participants With Significant Changes From Baseline in Physical Examination(Cycle 2 Day 1; End of the treatment.)
- Number of Participants With Eastern Cooperative Oncology Group (ECOG) Performance Status Shift to Grades 2, 3, 4 or 5(Screening (within 28 days prior to registration) up to 28 days (+7 days) after the last dose of study treatment)
- Maximum Observed Serum Concentration (Cmax) of PF-05082566-Cycle 5(Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.)
- Dose Normalized Cmax of PF-05082566-Cycle 5(Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.)
- Cmax of Mogamulizumab-Cycles 1 and 5(Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22; Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15)
- Pre-dose Concentration During Multiple Dosing (Ctrough) of PF-05082566-Cycle 5(Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.)
- Ctrough of Mogamulizumab- Cycle 5(Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15)
- Time for Cmax (Tmax) of PF-05082566-Cycle 5(Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.)
- Time of Last Measurable Concentration (Tlast) of PF-05082566-Cycle 5(Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.)
- Tmax of Mogamulizumab-Cycles 1 and 5(Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22; Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15)
- Tlast of Mogamulizumab-Cycles 1 and 5(Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22; Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15)
- Area Under the Serum Concentration-time Profile From Time 0 to the Time of the Last Measurable Concentration (AUClast) of PF-05082566-Cycle 5(Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.)
- Area Under the Serum Concentration-time Profile From Time 0 to 168 Hours (AUC168) of Mogamulizumab-Cycle 1(Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22)
- Dose Normalized AUClast of PF-05082566-Cycle 5(Cycle 5: Day 1 at pre-dose, at the end of PF-05082566 infusion, and at 2, 6, 168 hours (Day 8) and 336 hours (Day 15) after the start of PF-05082566 infusion.)
- AUClast of Mogamulizumab-Cycles 1 and 5(Cycle 1: pre-dose and at the end of mogamulizumab infusion on Days 1, 8, 15 and 22; Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15)
- Area Under the Serum Concentration-time Profile From Time 0 to Time Tau (AUCtau) of Mogamulizumab-Cycle 5(Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15)
- Clearance (CL) of Mogamulizumab-Cycle 5(Cycle 5: Pre-dose, at the end of mogamulizumab infusion, and at 6 hours, 168 hours (Day 8) after the start of the mogamulizumab infusion; Pre-dose on Day 15)
- Anti-Drug Antibody (ADA) Titer for PF-05082566(Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months)
- Anti-Drug Antibody (ADA) Titers for Mogamulizumab(Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months)
- Neutralizing Antibodies (NAb) Titers for PF-05082566(Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months)
- Neutralizing Antibodies (NAb) Titers for Mogamulizumab(Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 12, 16, 20, 24 up to 24 months)
- Number of Participants With Objective Response (OR) and Immune-related Objective Response (irOR)(Every 8 weeks up to 24 months)
- Time to Response (TTR) and Immue-related Time to Response (irTTR)-Dose Expansion Portion(Every 8 weeks up to 24 months)
- Duration of Response (DR) and Immune-related DR (irDR) -Dose Expansion Portion(Every 8 weeks from the first occurrence of CR or PR, until disease progression or death up to 24 months)
- Progression Free Survival (PFS) and Immune-related PFS (irPFS) - Dose Expansion Portion(Every 8 weeks up to 24 months)
研究者
研究点 (20)
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