Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)

About

Brief Summary

The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, when treating subjects with B-cell non-Hodgkin Lymphoma (B-NHL). The aim of the first part of the trial is to identify the most appropriate dose of epcoritamab, and the aim of the second part of the trial is to assess the selected epcoritamab dose in a larger group of participants with B-NHL. All participants in this trial will receive either epcoritamab alone, or epcoritamab combined with another standard treatment regimen, with a total of 10 different treatment arms being studied.

Trial details include:

The total trial duration will be up to 6 years.
The treatment duration for each participant depends upon which arm of treatment they are assigned to receive, but will be no more than 3 years.
The visit frequency for each participant depends upon which arm of treatment they are assigned to receive, but will be weekly to start for all participants, then will decrease to either: every 2 weeks, or every 3 weeks, or every 4 weeks, or every 8 weeks.
All participants will receive active drug; no one will be given placebo.

Participants who receive treatment with epcoritamab will have it injected right under the skin. Participants will receive a different regimen of epcoritamab depending upon which arm of treatment they are assigned.

Participants who receive standard treatments will have IV infusions and/or oral administration of those treatments. Participants will receive a different standard treatment regimen depending upon which arm of treatment they are assigned.

Arm 9 (follicular lymphoma (FL)) is still open for enrolment of new patients, while the other arms have closed their recruitment.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1/Phase 2

Eligibility

Gender

All

Healthy Volunteers

No

Minimum Age

18 Years

Maximum Age

N/A

Key Inclusion Criteria

Measurable disease defined as ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on computed tomography (CT) or magnetic resonance imaging (MRI)
Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
Acceptable organ function at screening
CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
If of childbearing potential subject must practicing a highly effective method of birth control
A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control Arm 1:

Newly diagnosed DLBCL
DLBCL, not otherwise specified (NOS)
"Double-hit" or "triple-hit" DLBCL
FL Grade 3B Arm 2: R/R FL Arm 3: Newly diagnosed, previously untreated FL grade 1-3A Arm 4:
Documented R/R DLBCL and eligible for HDT-ASCT
DLBCL, NOS
"Double-hit" or "triple-hit" DLBCL
FL Grade 3B Arm 5:
Documented R/R DLBCL and ineligible for HDT-ASCT
DLBCL, NOS
"Double-hit" or "triple-hit" DLBCL
FL Grade 3B Arm 6: Newly diagnosed, previously untreated FL grade 1-3A Arm 7:
FL Grade 1-3A
If PR or CR per Lugano criteria following first-line or second-line treatment with SOC regimen, and last dose of SOC within 6 months prior to enrollment. Arm 8:
Newly diagnosed DLBCL who are not fit to receive full-dose anthracycline
T-cell/histiocyte rich DLBCL
"Double-hit" or "triple-hit" DLBCL
FL Grade 3B Arm 9:
R/R FL
Progressed within 24 months of initiating first-line treatment Arm 10:
Documented R/R DLBCL and eligible for HDT-ASCT
DLBCL, NOS
"Double-hit" or "triple-hit" DLBCL
FL Grade 3B

Key Exclusion Criteria

Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
Any prior treatment with a bispecific antibody targeting CD3 and CD20.
Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab
Clinically significant cardiovascular disease
Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
CNS lymphoma or known CNS involvement by lymphoma at screening as confirmed by MRI/CT scan of the brain and, if clinically indicated, by lumbar puncture
Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
Known history of seropositivity of human immunodeficiency virus (HIV)
Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
Neuropathy > grade 1
Receiving immunostimulatory agent
Prior allogeneic HSCT
Current seizure disorder requiring anti-epileptic therapy