Study of VAY736 as Single Agent and in Combination With Select Antineoplastic Agents in Patients With Non-Hodgkin Lymphoma

Novartis

Status and phase: Enrolling; Phase 1

Conditions: Non-Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma

Treatments: Drug: VAY736; Drug: lenalidomide

Study type: Interventional

Funder types: Industry

Identifiers

NCT04903197

2020-005881-32 (EudraCT Number)

CVAY736J12101

Details and patient eligibility

About

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.

Full 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 will be explored alone or in combination with partner therapies. Increasing doses of VAY736 alone or in combination will be given to small groups of patients to identify the MTD/RD in patients with NHL. In dose expansion, some or all the treatments from dose escalation will be tested at the recommended doses in patients with NHL. Combination partners may be added in the future by protocol amendment. The study is expected to be approximately 4 years in duration (from enrollment of first patient to discontinuation of last patient).

Enrollment: 40 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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40 participants in 4 patient groups

Arm 1A

Experimental group

Description:

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)

Treatment:

Drug: VAY736

Arm 1B

Experimental group

Description:

VAY736 single agent dose expansion in patients with DLBCL

Treatment:

Drug: VAY736

Arm 2A

Experimental group

Description:

VAY736 + lenalidomide dose escalation in patients with DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL). Enrollment has been halted in this arm.

Treatment:

Drug: VAY736

Drug: lenalidomide

Arm 2B

Experimental group

Description:

VAY736 + lenalidomide dose expansion in patients with DLBCL. This arm will not be conducted.

Treatment:

Drug: VAY736

Drug: lenalidomide