Safety and Effectiveness Study of Epcoritamab Combinations for B-cell Non-Hodgkin Lymphoma

Sponsor: Genmab

Sponsor score: 40

Inactive

ClinicalTrials ID:NCT04663347

This study is testing the safety and effectiveness of a drug called epcoritamab, either alone or with other treatments, for people with B-cell non-Hodgkin Lymphoma (B-NHL). The study aims to find the best dose of epcoritamab and see how well it works in a larger group of patients.

Patient Parameters

Parameter	Options

Program Overview

The trial is designed to test how safe and effective epcoritamab is when used alone or with other treatments for B-cell non-Hodgkin Lymphoma (B-NHL). In the first part of the study, researchers will determine the best dose of epcoritamab. In the second part, they will test this dose in more patients. Participants will receive either epcoritamab by itself or combined with other standard treatments. There are 10 different treatment groups in the study. The trial will last up to 6 years, but each participant's treatment will last no more than 3 years. Initially, participants will have weekly visits, which will later become less frequent. Everyone in the study will receive active treatment, not a placebo.

Description

This study is a phase 1b/2 trial that is open to participants from multiple countries. It aims to evaluate the safety, how the body processes the drug, and the initial effectiveness of epcoritamab when used with other standard treatments for B-cell non-Hodgkin Lymphoma (B-NHL).

All participants will receive epcoritamab, either alone or with other treatments. The study includes the following treatment groups:

Group 1: Epcoritamab with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for untreated diffuse large B-cell lymphoma (DLBCL).
Group 2: Epcoritamab with rituximab and lenalidomide (R2) for relapsed or refractory (R/R) follicular lymphoma (FL).
Group 3: Epcoritamab with rituximab and bendamustine (BR) for untreated FL.
Group 4: Epcoritamab with rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin (R-DHAX/C) for R/R DLBCL eligible for stem cell transplant.
Group 5: Epcoritamab with gemcitabine and oxaliplatin (GemOx) for R/R DLBCL not eligible for stem cell transplant.
Group 6: Epcoritamab with R2 for untreated FL.
Group 7: Epcoritamab maintenance for FL patients who respond to standard treatment.
Group 8: Epcoritamab with a reduced dose of R-CHOP for untreated DLBCL not eligible for full-dose treatment.
Group 9: Epcoritamab with lenalidomide for second-line treatment in R/R FL.
Group 10: Epcoritamab with rituximab, ifosfamide, carboplatin, and etoposide phosphate (R-ICE) for R/R DLBCL eligible for stem cell transplant.

The study has two parts: Part 1 focuses on safety and includes Groups 1-5 and 10. Part 2 includes all groups and focuses on how well the treatment works, except for Group 7, which focuses on safety. Participants in Groups 1-5 and 10 can only join one part of the study. Safety will be closely monitored, especially in Part 1 and for some patients in Group 8.

Eligibility Criteria

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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

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