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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04903197

Collaborator

(none)

Enrollment

Locations

Arms

43.2

Anticipated Duration (Months)

8.6

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

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).

Study Design

Study Type:

Interventional

Anticipated 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 :

Jan 24, 2022

Anticipated Primary Completion Date :

Sep 1, 2025

Anticipated Study Completion Date :

Sep 1, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Ohio State University James Cancer Hospital &	Columbus	Ohio	United States	43210
2	MD Anderson Cancer Center	Houston	Texas	United States	77030
3	Novartis Investigative Site	Melbourne	Victoria	Australia	3004
4	Novartis Investigative Site	Tianjin	Tianjin	China	300020
5	Novartis Investigative Site	Koeln		Germany	50937
6	Novartis Investigative Site	Rozzano	MI	Italy	20089
7	Novartis Investigative Site	Koto ku	Tokyo	Japan	135 8550
8	Novartis Investigative Site	Yamagata		Japan	990 9585
9	Novartis Investigative Site	Seoul		Korea, Republic of	05505
10	Novartis Investigative Site	Madrid		Spain	28041