A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL

Study Overview
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Brief Summary
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The drug that will be investigated in the study is an antibody, epcoritamab, also known as EPKINLY™ and GEN3013. Since the safety and tolerability of epcoritamab has already been studied in previous studies in humans, the main purpose of this study is to evaluate efficacy. To evaluate this, half of the participants who are eligible will receive epcoritamab and the other half will receive a pre-specified investigator's choice of chemotherapy. Epcoritamab will be studied in R/R DLBCL participants who did not respond to a previous autologous stem cell transplant (ASCT) or do not meet the criteria for ASCT

Detailed Description
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The trial is an open label, multi-center, global phase 3 randomized trial of epcoritamab, GEN3013. The goal of this randomized trial is to evaluate the efficacy of epcoritamab (GEN3013, DuoBody®-CD3xCD20) compared to investigator's choice of chemotherapy, in patients with relapsed, refractory diffuse large B-Cell Lymphoma who have failed or are ineligible for high-dose chemotherapy and autologous stem cell transplant (HDT-ASCT). No change in chemotherapy is permitted for participants during the treatment phase of the trial.

Official Title
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A Randomized, Open-Label, Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in Relapsed/Refractory Diffuse Large B-cell Lymphoma (R/R DLBCL)

Conditions
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Diffuse Large B-cell Lymphoma

Intervention / Treatment
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* Biological: Epcoritamab
* Drug: Investigator's Choice Chemotherapy


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Relapsed or refractory disease and previously treated with at least 1 line of systemic antineoplastic therapy including anti-CD20 mAb-containing combination chemotherapy since lymphoma diagnosis One of the confirmed histologies below with CD20-positivity: DLBCL, NOS, including de novo or histologically transformed from FL Double-hit or triple-hit DLBCL (technically classified in WHO 2016 as HGBCL, with MYC and BCL2 and/or BCL6 translocations), including de novo or histologically transformed from FL FL Grade 3B T-cell/histiocyte-rich large B-cell lymphoma ECOG PS score of 0-2 Failed previous HDT-ASCT or not eligible for HDT-ASCT at screening Patients must have detectable disease by PET scan and measurable by CT scan or MRI Acceptable renal and liver function Life expectancy >2 months on SOC treatment Main Exclusion Criteria: Primary Central Nervous System (CNS) tumor or known CNS involvement Any prior therapy with a bispecific antibody targeting CD3 and CD20 Major surgery within 4 weeks prior to randomization Chemotherapy and other non-investigational antineoplastic agents (except CD20 mAbs) within 4 weeks or 5 half-lives (whichever is shorter) prior to randomization Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to randomization ASCT within 100 days of randomization Treatment with CAR-T therapy within 100 days prior to randomization Seizure disorder requiring anti-epileptic therapy Clinically significant cardiac disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Epcoritamab (GEN3013; DuoBody®CD3xCD20)<br>Epcoritamab will be administered in Cycles of 28 days until any of the discontinuation criteria is met | Biological: Epcoritamab<br>* Following mandatory pre-medication subject will be administered epcoritamab as a subcutaneous injection.<br>* Other names: EPKINLY™;|
| Active Comparator: Investigator's choice of chemotherapy<br>R-GemOx will be administrated in Cycles of 28 days until maximum cycles completion or any of the discontinuation criteria is met BR will be administrated in Cycles of 21 days until maximum cycles completion or any of the discontinuation criteria is met | Drug: Investigator's Choice Chemotherapy<br>* Following mandatory pre-medication subject will be administered intravenously either BR or R-GemOx.<br>* Other names: BR or R-GemOx;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | OS is calculated as the time from first dose to death date or last date known to be alive. | throughout the study and up to 5 years following the last patient first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | PFS is calculated as the time from randomization to the date of disease progression or death, whichever is earlier. Progression is determined by the Lugano criteria and LYRIC. | throughout the study and up to 5 years following the last patient first dose | 
| Overall Response Rate (ORR) | ORR is calculated as the proportion of subjects achieving a complete response or partial response. Response is determined by the Lugano criteria and LYRIC. | throughout the study and up to 5 years following the last patient first dose | 
| Complete Response (CR) | CR rate is calculated as the proportion of subjects achieving a complete response. Response is determined by the Lugano criteria and LYRIC. | throughout the study and up to 5 years following the last patient first dose | 
| Duration of Response (DOR) | DOR is calculated as the time from initial response (CR or PR) to date of progression or death, whichever is earlier. Response and progression are determined by the Lugano criteria and LYRIC. | throughout the study and up to 5 years following the last patient first dose | 
| Time to Response (TTR) | TTR is calculated as the time from randomization to date of initial response (CR or PR) among responders only. Response is determined by the Lugano criteria and LYRIC. | throughout the study and up to 5 years following the last patient first dose | 
| Rate and duration of minimal residual disease (MRD) negative status | Compare other measures of efficacy to SOC - MRD negativity rate, defined as the proportion of subjects who have at least one negative MRD sample at any time point prior to start of subsequent anti-lymphoma therapy | up to 5 years after randomization of the last patient | 
| Time to next anti-lymphoma therapy (TTNT) | TTNT is calculated as the time from randomization to date of initiation of new anti-lymphoma therapy. | throughout the study and up to 5 years following the last patient first dose | 
| Incidence and severity of adverse events (AEs) | identify patterns of incidence in adverse events, with particular emphasis on pre-defined adverse events of special interest | throughout the study and up to 5 years following the last patient first dose | 
| Incidence and severity of changes in laboratory values | Clinical laboratory parameters assessed: hematology, chemistry, coagulation, tumor lysis, immunoglobulins, and urinalyses | throughout the study and up to 5 years following the last patient first dose | 
| Incidence of dose interruptions and delays | calculate incidence and present the occurrence of dose modifying toxicities by cycles and overall | throughout the study and up to 5 years following the last patient first dose | 
| Anti-epcoritamab antibody response | calculate incidence of antibody response to epcoritamab in relation to dosing | throughout the study and up to 5 years following the last patient first dose | 
| Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) | monitor change from baseline in health-related quality of life over time and in relation to treatment | throughout the study and up to 5 years following the last patient first dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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double-hit DLBCL, triple-hit DLBCL, follicular grade 3B, transformed DLBCL, T-cell histiocytes-rich large B cell lymphoma