NCT02493751已完成1 期
A PHASE 1B, OPEN-LABEL, DOSE-FINDING STUDY TO EVALUATE SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF AVELUMAB (MSB0010718C) IN COMBINATION WITH AXITINIB (AG-013736) IN PATIENTS WITH PREVIOUSLY UNTREATED ADVANCED RENAL CELL CANCER
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 55
- 试验地点
- 20
- 主要终点
- Number of Participants With Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This is a Phase 1b, open-label, multi-center, multiple-dose trial designed to estimate the maximum tolerated dose (MTD) and select the recommended phase 2 dose (RP2D) of avelumab (MSB0010718C) in combination with axitinib (AG-013736). Once the MTD of avelumab administered in combination with axitinib is estimated (dose finding portion), the dose expansion phase will be opened to further characterize the combination in term of safety profile, anti tumor activity, pharmacokinetics, pharmacodynamics and biomarker modulation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 confirmed advanced RCC with clear cell component
- •Primary tumor resected
- •Availability of a recent formalin-fixed, paraffin-embedded (FFPE) tumor tissue block from a de novo tumor biopsy during screening (biopsied tumor lesion should not be a RECIST target lesion). Alternatively, a recently obtained archival FFPE tumor tissue block (not cut slides) from a primary or metastatic tumor resection or biopsy can be provided if the following criteria are met: 1) the biopsy or resection was performed within 1 year of enrollment AND 2) the patient has not received any intervening systemic anti-cancer treatment from the time the tissue was obtained and enrollment onto the current study. If an FFPE tissue block cannot be provided as per documented regulations,, 15 unstained slides (10 minimum) will be acceptable.
- •Availability of an archival FFPE tumor tissue block from primary diagnosis specimen (if available and not provided per above). If an FFPE tissue block cannot be provided, 15 unstained slides (10 minimum) will be acceptable
- •At least one measureable lesion as defined by RECIST version 1.1 that has not been previously irradiated.
- •Age ≥18 years (≥ 20 years in Japan).
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
- •Adequate bone marrow function, renal and liver functions
排除标准
- •Prior systemic therapy directed at advanced RCC.
- •Prior adjuvant or neoadjuvant therapy for RCC if disease progression or relapse has occurred during or within 12 months after the last dose of treatment
- •Prior immunotherapy with IL-2, IFN-α, or anti PD 1, anti PD L1, anti PD L2, anti CD137, or anti cytotoxic T lymphocyte associated antigen 4 (CTLA 4) antibody (including ipilimumab), or any other antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways
- •Prior therapy with axitinib as well as any prior therapies with other VEGF pathway inhibitors.
- •Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥3), any history of anaphylaxis.
- •Any of the following in the previous 6 months: myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack, deep vein thrombosis or symptomatic pulmonary embolism.
- •Vaccination within 4 weeks of the first dose of avelumab and while on trial is prohibited except for administration of inactivated vaccines (for example, inactivated influenza vaccines).
研究组 & 干预措施
Dose finding phase and dose expansion phase.
Experimental
To test the maximum tolerated dose of avelumab (MSB0010718C) in combination with axitinib (AG-013736)
干预措施: Avelumab (MSB0010718C) (Drug)
Dose finding phase and dose expansion phase.
Experimental
To test the maximum tolerated dose of avelumab (MSB0010718C) in combination with axitinib (AG-013736)
干预措施: Axitinib (AG-013736) (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicities (DLTs)
时间窗: DLT observation period (from the beginning of Cycle 1 up to the end of Cycle 2 [28 days])
DLT: greater than or equal to (\>=) Grade 3 hematologic/non-hematologic toxicity, Grade 3-4 liver-related laboratory test elevation (alanine aminotransferase, aspartate aminotransferase) with Grade 2 elevation of total bilirubin, non-hematologic Grade 3 laboratory abnormality (required medical intervention to treat participant/led to hospitalization), inability to complete \>=75% of first 2 cycles doses of axitinib (from Cycle 1 Day 1 after completion of lead-in period) or 2 infusions of avelumab within DLT observation period due to investigational product related toxicity.
次要结局
- Number of Participants With All-causality Treatment Emergent Adverse Events (TEAEs)(Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks))
- Time to Tumor Response (TTR) Based on RECIST Version 1.1(Cycle 1 Day 1 up to 30 months after the first dose)
- Time for Cmax (Tmax) for Axitinib When Dosed Alone and in Combination With Avelumab(Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1)
- Number of Participants With Treatment-related TEAEs(Baseline up to 30 days after the last dose of study treatment (maximum of 259.7 weeks))
- Change From Baseline in Vital Signs - Sitting Systolic Blood Pressure(Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD))
- Overall Survival (OS)(Cycle 1 Day 1 up to 30 months after the first dose)
- Maximum Observed Plasma Concentration (Cmax) for Axitinib When Dosed Alone and in Combination With Avelumab(Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1)
- Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Hematology(Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks))
- Number of Participants With Laboratory Abnormalities Graded by NCI CTCAE Version 4.03 - Chemistry(Baseline up to 30 days after the last dose of study treatment and 1 day before the start day of new anti-cancer drug therapy (maximum of 259.7 weeks))
- Change From Baseline in Vital Signs - Pulse Rate(Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD))
- Number of Participants Achieving Disease Control (DC) Based on RECIST Version 1.1(Cycle 1 Day 1 up to 30 months after the first dose)
- Progression-free Survival (PFS)(Cycle 1 Day 1 up to 30 months after the first dose)
- Area Under the Plasma Concentration Time Profile From Time Zero to the Next Dose at Steady State (AUCtau) for Axitinib When Dosed Alone and in Combination With Avelumab(Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1)
- Duration of Response (DR) Based on RECIST Version 1.1(Cycle 1 Day 1 up to 30 months after the first dose)
- Change From Baseline in Vital Signs - Sitting Diastolic Blood Pressure(Baseline, Day 1 of each cycle, Day 8 of Cycles 1 and 2, end of treatment, Follow-up Days 30, 60, 90 for all participants in the analysis population, and Lead-in Day 7 for participants with lead-in (maximum of 139.6 weeks by PCD))
- Number of Participants Achieving Objective Response (OR) Based on Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1(Cycle 1 Day 1 up to 30 months after the first dose)
- Predose Concentration During Multiple Dosing (Ctrough) for Avelumab(Predose on Day 1 of Cycles 1, 2, 3, 4, 6, 8, 14, 20, 26, 32, 38, 44, and 50)
- Number of Participants With Their Target Programmed Death-Ligand (PD-L1) Status at Baseline(Baseline)
- Terminal Half-Life (t1/2) for Axitinib When Dosed Alone and in Combination With Avelumab(Predose, 1, 2, 3, 4, 6, and 8 hours post dose on Lead-in Day 7 and Cycle 4 Day 1)
- Cmax for Avelumab(Predose, 1 hour, and 168 hours post dose on Cycle 1 Day 1; predose and 1 hour post dose on Cycle 4 Day 1)
- Number of Participants With Anti-drug Antibody (ADA) Against Avelumab When Combined With Axitinib by Never and Ever Positive Status(Pre-dose on Day 1 of Cycles 1-4, 6, 8, then every 12 weeks thereafter until Cycle 50, and on Follow-up Day 30 (maximum of 2 years))
研究者
研究点 (20)
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