A Phase Ib, Multi-center, Open-label Dose Escalation and Expansion Platform Study of VAY736 as Single Agent and in Combination With Select Antineoplastic Agents in Patients With Non-Hodgkin Lymphoma (NHL)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Incidence of Adverse events (AEs) and serious adverse events (SAEs)
研究概览
简要总结
The purpose of this study is to assess the safety, tolerability, pharmacokinetics (PK), immunogenicity and preliminary efficacy of VAY736 alone or in combination with other therapies in patients with NHL in a platform trial.
详细描述
The primary objective of the study is to evaluate the safety and tolerability in patients with NHL and identify a maximum tolerated dose (MTD) and/or recommended dose (RD) of VAY736 single agent and in combination with other anti-cancer therapies.
This is a phase I/Ib, multi-center, open-label study with multiple treatment arms in an adaptive study design. The study is comprised of a dose escalation part and dose expansion part.
In dose escalation, the investigational drug VAY736 was explored alone or in combination with lenalidomide. Increasing doses of VAY736 alone or in combination were given to small groups of patients to identify the maximum tolerated dose/recommended dose (MTD/RD) in patients with NHL. In dose expansion, some or all the treatments from dose escalation could be tested at the recommended doses in patients with NHL. The study was expected to last approximately 4 years (from the enrollment of the first patient to the discontinuation of the last patient), but it was terminated early due to a business decision, not because of any safety or tolerability concerns. Consequently, the dose expansion part was not conducted.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients with confirmed diagnosis of relapsed/refractory B-cell NHL with all subtypes of DLBCL, follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) per WHO 2016 criteria. Patients in subtype arm e.g. DLBCL must have confirmed diagnosis of relapsed/refractory DLBCL.
- •Received and failed or be intolerant to standard of care therapy (at least two prior lines, including an anti-CD20 therapy for NHL)
- •Must have measurable disease and ECOG of 0 to 2
排除标准
- •Baseline laboratory results outside of protocol defined ranges
- •Patients with primary CNS lymphoma
- •History of hypersensitivity to VAY736 or any drugs in similar chemical classes (e.g. monoclonal antibodies)
- •Impaired cardiac function or clinically significant cardiac disease
- •History of or current interstitial lung disease or pneumonitis grade 2 or higher
- •HIV infection
- •Active hepatitis C infection and/or hepatitis B infection
- •Pregnant or nursing (lactating) women
- •Women of child-bearing potential unless they are using highly effective methods of contraception
- •Other Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Arm 1A
VAY736 single agent dose escalation in patients with NHL subtypes of diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL)
干预措施: VAY736 (Drug)
Arm 1B
VAY736 single agent dose expansion in patients with DLBCL. This arm was not conducted.
干预措施: VAY736 (Drug)
Arm 2A
VAY736 + lenalidomide dose escalation in patients with DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL).
干预措施: VAY736 (Drug)
Arm 2A
VAY736 + lenalidomide dose escalation in patients with DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL).
干预措施: lenalidomide (Drug)
Arm 2B
VAY736 + lenalidomide dose expansion in patients with DLBCL. This arm was not conducted.
干预措施: VAY736 (Drug)
Arm 2B
VAY736 + lenalidomide dose expansion in patients with DLBCL. This arm was not conducted.
干预措施: lenalidomide (Drug)
结局指标
主要结局
Incidence of Adverse events (AEs) and serious adverse events (SAEs)
时间窗: 4 years
Incidence of AEs and SAEs is defined as number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms (ECGs) and laboratory results qualifying and reported as AEs.
Incidence and nature of dose limiting toxicities (DLTs)
时间窗: 28 days (first cycle of treatment)
Safety and tolerability
Number of patients with dose interruptions and dose reductions
时间窗: 4 years
Safety and tolerability
Dose intensity
时间窗: 4 years
Safety and tolerability
次要结局
- Maximum observed drug concentration after single dose administration (Cmax) for VAY736 and combination partners(4 years)
- Overall response rate (ORR)(4 years)
- Area under curve (AUC) for VAY736 and combination partners(4 years)
- Best overall response (BOR) rate(4 years)
- Change from baseline in anti-drug antibodies (ADA)(Baseline, 4 years)