Study of VAY736 as Single Agent and in Combination With Select Antineoplastic Agents in Patients With Non-Hodgkin Lymphoma
- Conditions
- Non-Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma
- Interventions
- Registration Number
- NCT04903197
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 18
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm 1A VAY736 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) Arm 1B VAY736 VAY736 single agent dose expansion in patients with DLBCL. This arm was not conducted. Arm 2A lenalidomide VAY736 + lenalidomide dose escalation in patients with DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL). Arm 2A VAY736 VAY736 + lenalidomide dose escalation in patients with DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL). Arm 2B VAY736 VAY736 + lenalidomide dose expansion in patients with DLBCL. This arm was not conducted. Arm 2B lenalidomide VAY736 + lenalidomide dose expansion in patients with DLBCL. This arm was not conducted.
- Primary Outcome Measures
Name Time Method Incidence of Adverse events (AEs) and serious adverse events (SAEs) 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) 28 days (first cycle of treatment) Safety and tolerability
Number of patients with dose interruptions and dose reductions 4 years Safety and tolerability
Dose intensity 4 years Safety and tolerability
- Secondary Outcome Measures
Name Time Method Maximum observed drug concentration after single dose administration (Cmax) for VAY736 and combination partners 4 years PK parameters will be derived from serum concentrations
Area under curve (AUC) for VAY736 and combination partners 4 years PK parameters will be derived from serum concentrations
Overall response rate (ORR) 4 years Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans)
Best overall response (BOR) rate 4 years Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans)
Change from baseline in anti-drug antibodies (ADA) Baseline, 4 years Blood samples will be collected to detect change in levels of antibodies to VAY736
Trial Locations
- Locations (1)
Novartis Investigative Site
🇸🇬Singapore, Singapore