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

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ClinicalTrials.gov Identifier: NCT04903197
Recruitment Status : Recruiting
First Posted : May 26, 2021
Last Update Posted : August 2, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( 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.

Condition or disease Intervention/treatment Phase
Non-Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma Drug: VAY736 Drug: lenalidomide Phase 1

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 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. The initial combination partner is lenalidomide. Other 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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 86 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
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)
Actual Study Start Date : January 24, 2022
Estimated Primary Completion Date : September 1, 2025
Estimated Study Completion Date : September 1, 2025


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.

Experimental: Arm 1B
VAY736 single agent dose expansion in patients with DLBCL
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.

Experimental: Arm 2A
VAY736 + lenalidomide dose escalation in patients with DLBCL
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.

Drug: lenalidomide
Immune-modulatory agent that enhances activation of NK cells.

Experimental: Arm 2B
VAY736 + lenalidomide dose expansion in patients with DLBCL
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.

Drug: lenalidomide
Immune-modulatory agent that enhances activation of NK cells.




Primary Outcome Measures :
  1. Incidence and nature of dose limiting toxicities (DLTs) [ Time Frame: 28 days (first cycle of treatment) ]
    Safety and tolerability

  2. Incidence of Adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: 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.

  3. Number of patients with dose interruptions and dose reductions [ Time Frame: 4 years ]
    Safety and tolerability

  4. Dose intensity [ Time Frame: 4 years ]
    Safety and tolerability


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: 4 years ]
    Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans)

  2. Best overall response (BOR) rate [ Time Frame: 4 years ]
    Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans)

  3. Area under curve (AUC) for VAY736 [ Time Frame: 4 years ]
    PK parameters will be derived from serum concentrations

  4. Maximum observed drug concentration after single dose administration (Cmax) for VAY736 [ Time Frame: 4 years ]
    PK parameters will be derived from serum concentrations

  5. AUC for lenalidomide [ Time Frame: 4 years ]
    PK parameters will be derived from plasma concentrations

  6. Cmax for lenalidomide [ Time Frame: 4 years ]
    PK parameters will be derived from plasma concentrations

  7. Change from baseline in anti-drug antibodies (ADA) [ Time Frame: Baseline, 4 years ]
    Blood samples will be collected to detect change in levels of antibodies to VAY736



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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, but no more than 5 prior lines)
  • Must have measurable disease and ECOG of 0 to 2
  • Must have a site of disease amenable to biopsy and be a candidate for tumor biopsy and be willing to undergo study required biopsies at screening and during therapy

Exclusion Criteria:

  • Baseline laboratory results outside of protocol defined ranges
  • Presence of history of central nervous system involvement by 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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04903197


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111

Locations
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United States, Ohio
The Ohio State University James Cancer Hospital & Recruiting
Columbus, Ohio, United States, 43210
Contact: Shayla Thompson    614-293-2268    Shayla.Thompson@osumc.edu   
Principal Investigator: David A Bond         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact    713-792-0007      
Principal Investigator: Jason Westin         
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3004
China, Tianjin
Novartis Investigative Site Recruiting
Tianjin, Tianjin, China, 300020
Germany
Novartis Investigative Site Recruiting
Koeln, Germany, 50937
Italy
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Japan
Novartis Investigative Site Recruiting
Koto ku, Tokyo, Japan, 135 8550
Novartis Investigative Site Recruiting
Yamagata, Japan, 990 9585
Korea, Republic of
Novartis Investigative Site Recruiting
Seoul, Korea, Republic of, 05505
Spain
Novartis Investigative Site Recruiting
Madrid, Spain, 28041
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Institutes of Biomedical Research Novartis Institutes of Biomedical Research
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04903197    
Other Study ID Numbers: CVAY736J12101
2020-005881-32 ( EudraCT Number )
First Posted: May 26, 2021    Key Record Dates
Last Update Posted: August 2, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
VAY736
non-Hodgkin lymphoma
NHL
DLBCL
FL
MCL
MZL
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, B-Cell
Lenalidomide
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents