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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Non-Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma
• Intervention / Treatment: Drug: VAY736; Drug: lenalidomide

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Novartis Investigative Site
• China
  • Shanghai, China, 200032
    • Novartis Investigative Site
  • Tianjin, China, 300020
    • Novartis Investigative Site
• Germany
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
• Italy
  • BS
    • Brescia, BS, Italy, 25123
      • Novartis Investigative Site
  • MI
    • Rozzano, MI, Italy, 20089
      • Novartis Investigative Site
• Japan
  • Yamagata
    • Yamagata, Yamagata, Japan, 990 9585
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119228
    • Novartis Investigative Site
• South Korea
  • Seoul, South Korea, 03080
    • Novartis Investigative Site
  • Seoul, South Korea, 05505
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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)	Drug: VAY736; VAY736 is a fully human IgG1 monoclonal antibody (mAb) which targets the B cell activating factor receptor (BAFF-R) expressed on the surface of differentiated B cells and modulates their function.; Other Names: ianalumab
Experimental: Arm 1B; VAY736 single agent dose expansion in patients with DLBCL. This arm was not conducted.	Drug: VAY736; VAY736 is a fully human IgG1 monoclonal antibody (mAb) which targets the B cell activating factor receptor (BAFF-R) expressed on the surface of differentiated B cells and modulates their function.; Other Names: ianalumab
Experimental: Arm 2A; VAY736 + lenalidomide dose escalation in patients with DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL).	Drug: VAY736; VAY736 is a fully human IgG1 monoclonal antibody (mAb) which targets the B cell activating factor receptor (BAFF-R) expressed on the surface of differentiated B cells and modulates their function.; Other Names: ianalumab; Drug: lenalidomide; Immune-modulatory agent that enhances activation of NK cells.
Experimental: Arm 2B; VAY736 + lenalidomide dose expansion in patients with DLBCL. This arm was not conducted.	Drug: VAY736; VAY736 is a fully human IgG1 monoclonal antibody (mAb) which targets the B cell activating factor receptor (BAFF-R) expressed on the surface of differentiated B cells and modulates their function.; Other Names: ianalumab; Drug: lenalidomide; Immune-modulatory agent that enhances activation of NK cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and nature of dose limiting toxicities (DLTs)	Safety and tolerability	28 days (first cycle of treatment)
Incidence of Adverse events (AEs) and serious adverse events (SAEs)	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.	4 years
Number of patients with dose interruptions and dose reductions	Safety and tolerability	4 years
Dose intensity	Safety and tolerability	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans)	4 years
Best overall response (BOR) rate	Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans)	4 years
Change from baseline in anti-drug antibodies (ADA)	Blood samples will be collected to detect change in levels of antibodies to VAY736	Baseline, 4 years
Area under curve (AUC) for VAY736 and combination partners	PK parameters will be derived from serum concentrations	4 years
Maximum observed drug concentration after single dose administration (Cmax) for VAY736 and combination partners	PK parameters will be derived from serum concentrations	4 years

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Novartis Institutes of Biomedical Research, Novartis Institutes of Biomedical Research

Publications and helpful links

Helpful Links

• CVAY736J12101 Clinical Trial Results
• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2022
• Primary Completion (Actual): February 24, 2025
• Study Completion (Actual): February 24, 2025

Study Registration Dates

• First Submitted: May 25, 2021
• First Submitted That Met QC Criteria: May 25, 2021
• First Posted (Actual): May 26, 2021

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Diffuse large B cell lymphoma; lenalidomide; DLBCL; NHL; VAY736; non-Hodgkin lymphoma; FL; MCL; MZL; Follicular lymphoma; Mantle cell lymphoma; Marginal zone lymphoma; ianalumab
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, B-Cell; Lymphoma; Hemic and Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, B-Cell, Marginal Zone; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide; ianalumab
• Other Study ID Numbers: CVAY736J12101; 2020-005881-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No