A Phase I/Ib, Open-label, Multi-center, Study of KAZ954 as a Single Agent and in Combination With Spartalizumab, NZV930 and NIR178 in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 77
- 试验地点
- 6
- 主要终点
- Incidence of Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The primary objective of the trial was to characterize the safety, tolerability, and maximum tolerated dose (MTD)/recommended dose (RD) for expansion of single agent KAZ954 and KAZ954 in combination with PDR001, NIR178 and NZV930.
详细描述
The purpose of this trial was to explore the clinical utility of several therapies in patients with advanced cancer.
This is a multi-center, open-label Phase I/Ib study. The study consisted of a dose escalation part and a dose expansion part testing KAZ954 as a single agent or KAZ954 in combination with PDR001, NZV930 and NIR178.
The dose escalation part estimated the MTD and/or RD and tested different dosing schedules. The dose escalation arm KAZ954 + NZV930 was not opened.
The dose expansion part of the study was planned to use the MTD/RDE determined in the dose escalation part to assess the activity, safety and tolerability of the investigational products in patients with specific types of cancer. The dose expansion part of the study was not started.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with metastatic and/or advanced malignancies not amenable to curative treatment by surgery.
- •Must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines. Patient must be willing to undergo a new tumor biopsy at screening and during the study.
- •ECOG Performance Status of <2.
排除标准
- •Presence of symptomatic central nervous system (CNS) metastases, or CNS metastases that require concurrent treatment - including surgery, radiation and/or corticosteroids.
- •History of severe hypersensitivity reaction to any ingredient of study drug(s) and other mAbs and/or their excipients.
- •Impaired cardiac function HIV Known history of tuberculosis Systemic chronic steroid therapy
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Arm A
KAZ954
干预措施: KAZ954 (Drug)
Arm B
KAZ954 + PDR001
干预措施: KAZ954 (Drug)
Arm B
KAZ954 + PDR001
干预措施: PDR001 (Drug)
Arm C
KAZ954 + NIR178
干预措施: KAZ954 (Drug)
Arm C
KAZ954 + NIR178
干预措施: NIR178 (Drug)
Arm D
KAZ954 + NZV930
干预措施: KAZ954 (Drug)
Arm D
KAZ954 + NZV930
干预措施: NZV930 (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities (DLTs)
时间窗: Up to 35 days
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade ≥ 3 assessed as unrelated to disease, disease progression, inter-current illness or concomitant medications, which occurs within the DLT period. The DLT period for Schedule 1 is 28 days and covers two infusions. The DLT period for Schedule 2 and Schedule 3 is 35 days to cover two infusions of the Experimental dose. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Dose intensity of study treatment
时间窗: Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178)
Dose intensity of KAZ954 and its combination partners computed as the ratio of actual cumulative dose received and actual duration of exposure.
Number of participants with dose interruptions and dose reductions
时间窗: Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178)
Number of participants with at least one dose interruption or reduction of KAZ954 and its combination partners during study treatment to assess tolerability.
Incidence of adverse events and serious adverse events during the on-treatment period
时间窗: Up to approximately 52 weeks (KAZ954 single agent), 20 weeks (KAZ954+PDR001) and 24 weeks (KAZ954+NIR178)
Number of participants with AEs (any AE regardless of seriousness) and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. The on-treatment period is defined from the day of first administration of study treatment up to 30 days after the date of its last administration.
次要结局
- Maximum observed plasma concentration (Cmax) of NIR178 and its metabolite NJI765(Cycle 1 Day 1 (C1D1) and Cycle 2 Day 1 (C2D1): pre-dose, 15 minutes, 1, 2, 4 and 6 hours after morning dose and 12 hours after evening dose. One cycle=28 days)
- Overall Response Rate (ORR) using RECIST v1.1 and iRECIST by PD-L1 expression(Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178))
- Progression-Free Survival (iPFS) per iRECIST(Up to approximately 52 weeks (KAZ954 single agent), 20 weeks (KAZ954+PDR001) and 24 weeks (KAZ954+NIR178))
- Maximum observed serum concentration (Cmax) of KAZ954(Cycle 1 Day 1 (C1D1) and Cycle 3 Day 1 (C3D1): pre-dose, 1, 24, 72, 168, 240 and 360 hours after the end of the infusion. The duration of the infusion was 2 hours. One cycle=28 days)
- Number of participants with anti-KAZ954 antibodies(Baseline (before first dose) and post-baseline (assessed throughout the treatment, up to approximately 48 weeks, 16 weeks and 20 weeks for KAZ954 single agent, KAZ954+PDR001 and KAZ954+NIR178, respectively))
- Progression Free Survival (PFS) using RECIST v1.1 and iRECIST by PD-L1 expression(Up to approximately 52 weeks (KAZ954 single agent), 20 weeks (KAZ954+PDR001) and 24 weeks (KAZ954+NIR178))
- Disease Control Rate (DCR) per iRECIST(Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178))
- Maximum observed serum concentration (Cmax) of PDR001(Cycle 1 Day 1 (C1D1) and Cycle 3 Day 1 (C3D1): pre-dose, 1, 168, 336 and 672 hours after the end of the infusion. The duration of the infusion was 30 minutes. One cycle=28 days)
- Area under the plasma concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of NIR178 and its metabolite NJI765(Cycle 1 Day 1 (C1D1) and Cycle 2 Day 1 (C2D1): pre-dose, 15 minutes, 1, 2, 4 and 6 hours after morning dose and 12 hours after evening dose. One cycle=28 days)
- Overall Response Rate (ORR) per RECIST v1.1(Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178))
- Progression-Free Survival (PFS) per RECIST v1.1(Up to approximately 52 weeks (KAZ954 single agent), 20 weeks (KAZ954+PDR001) and 24 weeks (KAZ954+NIR178))
- Area under the serum concentration-time curve from time zero to 14 days post dose (AUC0-14d) of KAZ954(Cycle 1 Day 1 (C1D1) and Cycle 3 Day 1 (C3D1): pre-dose, 1, 24, 72, 168, 240 and 360 hours after the end of the infusion. The duration of the infusion was 2 hours. One cycle=28 days)
- Number of participants with anti-PDR001 antibodies(Baseline (before first dose) and post-baseline (assessed throughout the treatment, up to approximately 16 weeks))
- Overall Response Rate (ORR) per iRECIST(Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178))
- Disease Control Rate (DCR) per RECIST v1.1(Up to approximately 48 weeks (KAZ954 single agent), 16 weeks (KAZ954+PDR001) and 20 weeks (KAZ954+NIR178))
- Area under the serum concentration-time curve from time zero to the time of the last quantifiable concentration (AUClast) of PDR001(Cycle 1 Day 1 (C1D1) and Cycle 3 Day 1 (C3D1): pre-dose, 1, 168, 336 and 672 hours after the end of the infusion. The duration of the infusion was 30 minutes. One cycle=28 days)