NCT02511184终止1 期
A PHASE 1B STUDY OF CRIZOTINIB IN COMBINATION WITH PEMBROLIZUMAB (MK-3475) IN PATIENTS WITH UNTREATED ADVANCED ALK-TRANSLOCATED NON SMALL CELL LUNG CANCER
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
- 9
- 试验地点
- 14
- 主要终点
- Number of Participants With Dose-limiting Toxicity (DLT)
研究概览
简要总结
The purpose of this study has 2 phases, a Dose Finding Phase will determine the maximum tolerated dose . The Dose Expansion Phase will explore the safety, tolerability, and anti-tumor activity of the combination.
详细描述
The patients will be screened for up to 28 days before they start treatment to determine if they meet eligibility criteria. The screening procedures will include physical examination, blood work and radiological scans.
In the dose finding phase, patients who meet eligibility criteria will receive crizotinib at the dose level assigned that will be taken on daily basis and pembrolizumab 200 mg intravenous infusion every 3 weeks.
Once a Crizotinib dose level is decided, the dose expansion cohort will start enrolling patients who meet eligibility criteria.
All patients will be followed up every three weeks. Blood samples will be drawn to test for safety and tumor activities and radiological scans will be performed on certain timepoints to determine the antitumor activities.
There will be a quality of life questionnaire administered at certain time points during the study.
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
- •Histologically or cytologically proved diagnosis of locally advanced recurrent or metastatic non-squamous NSCLC that is not suitable for local curative treatment.
- •Alk-positive NSCLC as determined by a test that is approved or validated for use as a companion diagnostic test.
- •No prior systemic therapy for metastatic disease.
- •Adjuvant chemotherapy more than 12 months prior to study enrollment.
- •Measurable disease as per RECIST 1.1
- •ECOG PS 0 or 1.
排除标准
- •Prior exposure to ALK receptor tyrosine kinase inhibitor, anti-PD1, anti-PDL1 or any drug targeting T-cell checkpoint pathways.
- •known diagnosis of immunodeficiency or is receiving systemic steroid therapy or other form of immunosuppressive therapy within 7 days of clinical trial treatment.
- •Active autoimmune disease that has required systemic treatment in the past 3 months.
- •History of extensive disseminated interstitial fibrosis or any grade of interstitial lung disease.
研究组 & 干预措施
Dose finding and dose expansion phases
Experimental
Find and expand the maximum tolerated dose of crizotinib in combination with pembrolizumab 200 mg iv infusion every 3 weeks.
干预措施: Crizotinib (Drug)
Dose finding and dose expansion phases
Experimental
Find and expand the maximum tolerated dose of crizotinib in combination with pembrolizumab 200 mg iv infusion every 3 weeks.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Number of Participants With Dose-limiting Toxicity (DLT)
时间窗: 6 weeks
Dose-limiting toxicity (DLT) was defined as any of the following adverse events (AEs) occurring in the first 2 cycles of treatment (6 weeks) which were attributable to crizotinib, pembrolizumab or both: hematologic toxicities including Grade 4 neutropenia, febrile neutropenia, Grade greater than or equal to (\>=) 3 neutropenic infection, Grade \>=3 thrombocytopenia with bleeding; Grade 4 thrombocytopenia; non-hematologic toxicities including Grade \>=3 toxicities (non-laboratory), Grade \>=3 nausea, vomiting, or diarrhea despite maximal therapy, non-hematologic Grade \>=3 laboratory value if medical intervention was required to treat the participant or the abnormality led to hospitalization; inability to complete at least 80 percent of the first 2-cycle doses of crizotinib or both infusions of pembrolizumab within the DLT observation period due to treatment-related toxicity. Grade was based on National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) version 4.03.
次要结局
- Objective Response Rate (ORR)(Baseline, Week 9 and every 6 weeks thereafter, for about 2 years)
- Duration of Response(Baseline, Week 9 and every 6 weeks thereafter, for about 2 years)
- Time to Tumor Response(Baseline, Week 9 and every 6 weeks thereafter, for about 2 years)
- Number of Participants With Treatment-Emergent Adverse Events(2 years)
- Progression Free Survival(Baseline, Week 9 and every 6 weeks thereafter, for about 2 years)
- 6-Month, 12-Month and 18-Month Progression Free Survival Probabilities(Month 6, Month 12, and Month 18)
- Overall Survival(Day 1 to end of study (for about 2 years))
- 12-Month and 18-Month Overall Survival Probabilities(Month 12 and Month 18)
- Number of Participants With Maximum Grade in Laboratory Hematology Test Shifting From Grade 0, 1 or 2 at Baseline to Grade 3 or 4 During Treatment(2 years)
- Number of Participants With Maximum Grade in Laboratory Chemistry Test Shifting From Grade 0, 1 or 2 at Baseline to Grade 3 or 4 During Treatment(2 years)
- Plasma Concentration Summary of Crizotinib for "Crizotinib + Pembrolizumab" Group(Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment))
- Plasma Concentration Summary of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group(Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment))
- Time to Maximum Plasma Concentration (Tmax) of Crizotinib for "Crizotinib + Pembrolizumab" Group(Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment))
- Time to Maximum Plasma Concentration (Tmax) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group(Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment))
- Area Under the Plasma Concentration Time Curve From 0 to 8 Hours (AUC0-8) of Crizotinib for "Crizotinib + Pembrolizumab" Group(Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment))
- Area Under the Plasma Concentration Time Curve From 0 to 8 Hours (AUC0-8) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group(Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment))
- Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of Crizotinib for "Crizotinib + Pembrolizumab" Group(Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment))
- Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group(Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment))
- Apparent Plasma Clearance (CL/F) of Crizotinib for "Crizotinib + Pembrolizumab" Group(Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment))
- Apparent Plasma Clearance (CL/F) of Crizotinib for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group(Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment))
- Plasma Concentration Summary of PF-06260182 for "Crizotinib + Pembrolizumab" Group(Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment))
- Plasma Concentration Summary of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group(Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment))
- Time to Maximum Plasma Concentration (Tmax) of PF-06260182 for "Crizotinib + Pembrolizumab" Group(Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment))
- Time to Maximum Plasma Concentration (Tmax) of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group(Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment))
- Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of PF-06260182 for "Crizotinib + Pembrolizumab" Group(Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment))
- Area Under the Plasma Concentration Time Curve Over the Dosing Interval (AUCtau) of PF-06260182 for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group(Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment))
- Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib + Pembrolizumab" Group(Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment))
- Metabolite (PF-06260182) to Parent (Crizotinib) Concentration Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group(Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment))
- Serum Concentration of Pembrolizumab(Prior to and at end of pembrolizumab infusion, 120 hours and 336 hours post Day 1 dosing of Cycle 1; pre-dose on Day 1 of Cycles 2, 4,6, 8, 12 and 16; end of Day 1 dosing of Cycle 8; End of Treatment visit)
- Number of Participants With Programmed Death Receptor-1 Ligand-1 (PD-L1) Expression Level Meeting Pre-defined Criteria(Screening)
- Metabolite (PF-06260182) to Parent (Crizotinib) AUCtau Ratio for "Crizotinib + Pembrolizumab" Group(Prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28 to 35 days after the last dose of study treatment))
- Metabolite (PF-06260182) to Parent (Crizotinib) AUCtau Ratio for "Crizotinib Monotherapy Followed by Crizotinib + Pembrolizumab" Group(Pre-dose, and 1, 2, 4, 6 and 8 hours post-dose on Day 15 of monotherapy and on Day 1 of Cycle 6; prior to crizotinib morning dose on Day 1 of Cycles 1, 2, 4, 6, and 8, and at the End of Treatment visit (28-35 days after the last dose of study treatment))
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