search
Back to results

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

Primary Purpose

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

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
VAY736
lenalidomide
CC-99282
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma focused on measuring VAY736, ianalumab, lenalidomide, CC-99282, golcadomide, BMS-986369, non-Hodgkin lymphoma, NHL, Diffuse large B cell lymphoma, DLBCL, Follicular lymphoma, FL, Mantle cell lymphoma, MCL, Marginal zone lymphoma, MZL

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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, 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

Sites / Locations

  • City of Hope National Med CtrRecruiting
  • The Ohio State University James Cancer Hospital &Recruiting
  • MD Anderson Cancer CenterRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative Site
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Arm 1A

Arm 1B

Arm 2A

Arm 2B

Arm 3A

Arm 3B

Arm 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)

VAY736 single agent dose expansion in patients with DLBCL

VAY736 + lenalidomide dose escalation in patients with DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL)

VAY736 + lenalidomide dose expansion in patients with DLBCL

VAY736 + CC-99282 dose escalation in patients with NHL subtypes of DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL)

VAY736 + CC-99282 dose expansion in patients with DLBCL

Outcomes

Primary Outcome Measures

Incidence and nature of dose limiting toxicities (DLTs)
Safety and tolerability
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.
Number of patients with dose interruptions and dose reductions
Safety and tolerability
Dose intensity
Safety and tolerability

Secondary Outcome Measures

Overall response rate (ORR)
Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans)
Best overall response (BOR) rate
Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans)
Area under curve (AUC) for VAY736
PK parameters will be derived from serum concentrations
Maximum observed drug concentration after single dose administration (Cmax) for VAY736
PK parameters will be derived from serum concentrations
AUC for lenalidomide
PK parameters will be derived from plasma concentrations
Cmax for lenalidomide
PK parameters will be derived from plasma concentrations
Change from baseline in anti-drug antibodies (ADA)
Blood samples will be collected to detect change in levels of antibodies to VAY736
AUC for CC-99282
PK parameters will be derived from plasma concentrations
Cmax for CC-99282
PK parameters will be derived from plasma concentrations

Full Information

First Posted
May 25, 2021
Last Updated
September 20, 2023
Sponsor
Novartis Pharmaceuticals
Collaborators
Bristol-Myers Squibb
search

1. Study Identification

Unique Protocol Identification Number
NCT04903197
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 24, 2022 (Actual)
Primary Completion Date
June 30, 2027 (Anticipated)
Study Completion Date
June 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals
Collaborators
Bristol-Myers Squibb

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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 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 combination partners include lenalidomide and CC-99282. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma, Follicular Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma
Keywords
VAY736, ianalumab, lenalidomide, CC-99282, golcadomide, BMS-986369, non-Hodgkin lymphoma, NHL, Diffuse large B cell lymphoma, DLBCL, Follicular lymphoma, FL, Mantle cell lymphoma, MCL, Marginal zone lymphoma, MZL

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
124 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm 1A
Arm Type
Experimental
Arm 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)
Arm Title
Arm 1B
Arm Type
Experimental
Arm Description
VAY736 single agent dose expansion in patients with DLBCL
Arm Title
Arm 2A
Arm Type
Experimental
Arm Description
VAY736 + lenalidomide dose escalation in patients with DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL)
Arm Title
Arm 2B
Arm Type
Experimental
Arm Description
VAY736 + lenalidomide dose expansion in patients with DLBCL
Arm Title
Arm 3A
Arm Type
Experimental
Arm Description
VAY736 + CC-99282 dose escalation in patients with NHL subtypes of DLBCL, follicular lymphoma (FL), mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL)
Arm Title
Arm 3B
Arm Type
Experimental
Arm Description
VAY736 + CC-99282 dose expansion in patients with DLBCL
Intervention Type
Drug
Intervention Name(s)
VAY736
Other Intervention Name(s)
ianalumab
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
lenalidomide
Intervention Description
Immune-modulatory agent that enhances activation of NK cells.
Intervention Type
Drug
Intervention Name(s)
CC-99282
Other Intervention Name(s)
BMS-986369, golcadomide
Intervention Description
Cereblon (CRBN) E3 Ligase Modulator that induces the recruitment, ubiquitination and destruction of key target substrates (e.g. Ikaros family zinc finger proteins 1 and 3 (IKZF1 and IKZF3)
Primary Outcome Measure Information:
Title
Incidence and nature of dose limiting toxicities (DLTs)
Description
Safety and tolerability
Time Frame
28 days (first cycle of treatment)
Title
Incidence of Adverse events (AEs) and serious adverse events (SAEs)
Description
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.
Time Frame
4 years
Title
Number of patients with dose interruptions and dose reductions
Description
Safety and tolerability
Time Frame
4 years
Title
Dose intensity
Description
Safety and tolerability
Time Frame
4 years
Secondary Outcome Measure Information:
Title
Overall response rate (ORR)
Description
Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans)
Time Frame
4 years
Title
Best overall response (BOR) rate
Description
Efficacy will be assessed by Lugano Classification (FDG-PET/CT scans)
Time Frame
4 years
Title
Area under curve (AUC) for VAY736
Description
PK parameters will be derived from serum concentrations
Time Frame
4 years
Title
Maximum observed drug concentration after single dose administration (Cmax) for VAY736
Description
PK parameters will be derived from serum concentrations
Time Frame
4 years
Title
AUC for lenalidomide
Description
PK parameters will be derived from plasma concentrations
Time Frame
4 years
Title
Cmax for lenalidomide
Description
PK parameters will be derived from plasma concentrations
Time Frame
4 years
Title
Change from baseline in anti-drug antibodies (ADA)
Description
Blood samples will be collected to detect change in levels of antibodies to VAY736
Time Frame
Baseline, 4 years
Title
AUC for CC-99282
Description
PK parameters will be derived from plasma concentrations
Time Frame
4 years
Title
Cmax for CC-99282
Description
PK parameters will be derived from plasma concentrations
Time Frame
4 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Institutes of Biomedical Research
Organizational Affiliation
Novartis Institutes of Biomedical Research
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope National Med Ctr
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jessica Flores
Phone
+1 6263598111#65994
Email
jesflores@coh.org
First Name & Middle Initial & Last Name & Degree
Swetha Kambhampati
Facility Name
The Ohio State University James Cancer Hospital &
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shayla Thompson
Phone
614-293-2268
Email
Shayla.Thompson@osumc.edu
First Name & Middle Initial & Last Name & Degree
David A Bond
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Carolyn Hawkins
Phone
713-792-0007
Email
chawkins@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Jason Westin
Facility Name
Novartis Investigative Site
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210029
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200032
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Gottingen
ZIP/Postal Code
37075
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Koeln
ZIP/Postal Code
50937
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Brescia
State/Province
BS
ZIP/Postal Code
25123
Country
Italy
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Milano
State/Province
MI
ZIP/Postal Code
20133
Country
Italy
Individual Site Status
Withdrawn
Facility Name
Novartis Investigative Site
City
Rozzano
State/Province
MI
ZIP/Postal Code
20089
Country
Italy
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Koto ku
State/Province
Tokyo
ZIP/Postal Code
135 8550
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Yamagata
ZIP/Postal Code
990 9585
Country
Japan
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28034
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Madrid
ZIP/Postal Code
28041
Country
Spain
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs