A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL
- Conditions
- Diffuse Large B-cell Lymphoma
- Interventions
- Drug: Investigator's Choice Chemotherapy
- Registration Number
- NCT04628494
- Lead Sponsor
- Genmab
- Brief Summary
The purpose of this trial is to find out if epcoritamab, also known as EPKINLY™ and GEN3013, is safe and works well as treatment for patients with diffuse large B-cell lymphoma (DLBCL) that are not responding to treatment, have grown in size, or have come back following treatment with at least 1 prior systemic cancer therapy. All participants in this trial will be randomly assigned to receive either epcoritamab or a pre-specified investigator's choice (standard of care) chemotherapy (either rituximab + gemcitabine + oxaliplatin \[R-GemOx\], or bendamustine + rituximab \[BR\]). Participants must have failed or be ineligible to receive an autologous stem cell transplant (ASCT).
Epcoritamab will be injected under the skin. Investigator's choice chemotherapy will be given intravenously.
Trial details include:
* The trial duration will be up to 5 years after last participant is randomized.
* All trial participants have a 21-day screening period, a treatment period, and a follow-up period that continues until death.
* The estimated trial duration for an individual subject depends upon the treatment arm assigned:
* Participants who receive epcoritamab will have 28-day treatment cycles. Epcoritamab will be given once weekly for the first 3 months, then every other week for 6 months, then every 28 days until lymphoma progression or unacceptable adverse events.
* Participants who receive investigator's choice (standard of care) chemotherapy will receive treatments either:
* R-GemOx: On Day 1 (or Day 1 \& Day 2), and Day 15 (or Day 15 \& Day 16) every 28 days, for up to 4 months; or
* BR: On Day 1 and Day 2 every 3 weeks for up to 4.5 months.
- Detailed Description
The trial is an open label, multi-center, global phase-3 randomized trial of epcoritamab. 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 DLBCL 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 552
-
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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Investigator's choice of chemotherapy Investigator's Choice Chemotherapy 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 Epcoritamab (GEN3013; DuoBody®CD3xCD20) Epcoritamab Epcoritamab will be administered in Cycles of 28 days until any of the discontinuation criteria is met
- Primary Outcome Measures
Name Time Method Overall Survival (OS) throughout the study and up to 5 years following the last patient first dose OS is calculated as the time from first dose to death date or last date known to be alive.
- Secondary Outcome Measures
Name Time Method Complete Response (CR) throughout the study and up to 5 years following the last patient first dose CR rate is calculated as the proportion of subjects achieving a complete response. Response is determined by the Lugano criteria and LYRIC.
Duration of Response (DOR) throughout the study and up to 5 years following the last patient first dose 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.
Time to Response (TTR) throughout the study and up to 5 years following the last patient first dose 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.
Progression Free Survival (PFS) throughout the study and up to 5 years following the last patient first dose 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.
Incidence and severity of adverse events (AEs) throughout the study and up to 5 years following the last patient first dose identify patterns of incidence in adverse events, with particular emphasis on pre-defined adverse events of special interest
Anti-epcoritamab antibody response throughout the study and up to 5 years following the last patient first dose calculate incidence of antibody response to epcoritamab in relation to dosing
Incidence and severity of changes in laboratory values throughout the study and up to 5 years following the last patient first dose Clinical laboratory parameters assessed: hematology, chemistry, coagulation, tumor lysis, immunoglobulins, and urinalyses
Incidence of dose interruptions and delays throughout the study and up to 5 years following the last patient first dose calculate incidence and present the occurrence of dose modifying toxicities by cycles and overall
Overall Response Rate (ORR) throughout the study and up to 5 years following the last patient first dose ORR is calculated as the proportion of subjects achieving a complete response or partial response. Response is determined by the Lugano criteria and LYRIC.
Rate and duration of minimal residual disease (MRD) negative status up to 5 years after randomization of the last patient 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
Time to next anti-lymphoma therapy (TTNT) throughout the study and up to 5 years following the last patient first dose TTNT is calculated as the time from randomization to date of initiation of new anti-lymphoma therapy.
Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) throughout the study and up to 5 years following the last patient first dose monitor change from baseline in health-related quality of life over time and in relation to treatment
Trial Locations
- Locations (208)
Indiana Blood and Marrow Transplantation
🇺🇸Indianapolis, Indiana, United States
Community Health Network Cancer Center North
🇺🇸Indianapolis, Indiana, United States
University of Kentucky Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Henry Ford Health System
🇺🇸Jackson, Michigan, United States
MMCORC Attn Delaney Anderson
🇺🇸Saint Louis Park, Minnesota, United States
MD Anderson Cancer Center at Cooper
🇺🇸Camden, New Jersey, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
The Christ Hospital Cancer Center
🇺🇸Cincinnati, Ohio, United States
TriHealth Cancer Institute- Good Samaritan Hospital
🇺🇸Cincinnati, Ohio, United States
Brooke Army Medical Center
🇺🇸Fort Sam Houston, Texas, United States
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