Clinical trial NCT04903197: Study of VAY736 as Single Agent and in Combination With Select Antineoplastic Agents in Patients With Non-Hodgkin Lymphoma
Official title: 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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Non-Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma
Keywords: VAY736
ianalumab
lenalidomide
non-Hodgkin lymphoma
NHL
Diffuse large B cell lymphoma
DLBCL
Follicular lymphoma
FL
Mantle cell lymphoma
MCL
Marginal zone lymphoma
MZL
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2021-05-26
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Incidence and nature of dose limiting toxicities (DLTs)
timeFrame: 28 days (first cycle of treatment)
measure: Incidence of Adverse events (AEs) and serious adverse events (SAEs)
timeFrame: 4 years
measure: Number of patients with dose interruptions and dose reductions
timeFrame: 4 years
measure: Dose intensity
timeFrame: 4 years
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: 4 years
measure: Best overall response (BOR) rate
timeFrame: 4 years
measure: Area under curve (AUC) for VAY736 and combination partners
timeFrame: 4 years
measure: Maximum observed drug concentration after single dose administration (Cmax) for VAY736 and combination partners
timeFrame: 4 years
measure: Change from baseline in anti-drug antibodies (ADA)
timeFrame: Baseline, 4 years
Other outcomes:
Locations:
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Shanghai
country: China
facility: Novartis Investigative Site
city: Tianjin
country: China
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Rozzano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Yamagata
country: Japan
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Institutes of Biomedical Research
name: Novartis Institutes of Biomedical Research
role: STUDY_DIRECTOR
References: