A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL (EPCORE DLBCL-1)

• ClinicalTrials.gov Identifier: NCT04628494
• Recruitment Status: Recruiting
• First Posted: November 13, 2020
• Last Update Posted: January 11, 2023
• Sponsor: Genmab
• Collaborator: AbbVie
• Information provided by (Responsible Party): Genmab

Tracking Information

• First Submitted Date: November 9, 2020
• First Posted Date: November 13, 2020
• Last Update Posted Date: January 11, 2023
• Actual Study Start Date: January 13, 2021
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 27, 2022)

Overall Survival (OS) [ Time Frame: throughout the study and up to 2 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.

Original Primary Outcome Measures (submitted: November 9, 2020)

Compare the clinical efficacy of epcoritamab to standard of care (SOC) - Overall Survival (OS) [ Time Frame: throughout the study and up to 2 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.

Current Secondary Outcome Measures (submitted: April 27, 2022)

• Progression Free Survival (PFS) [ Time Frame: throughout the study and up to 2 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.
• Overall Response Rate (ORR) [ Time Frame: throughout the study and up to 2 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.
• Complete Response (CR) [ Time Frame: throughout the study and up to 2 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) [ Time Frame: throughout the study and up to 2 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) [ Time Frame: throughout the study and up to 2 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.
• Rate and duration of minimal residual disease (MRD) negative status [ Time Frame: up to 2 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) [ Time Frame: throughout the study and up to 2 years following the last patient first dose ]
  TTNT is calculated as the time from randomization to date of initiation of new anti-lymphoma therapy.
• Incidence and severity of adverse events (AEs) [ Time Frame: throughout the study and up to 2 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
• Incidence and severity of changes in laboratory values [ Time Frame: throughout the study and up to 2 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 [ Time Frame: throughout the study and up to 2 years following the last patient first dose ]
  calculate incidence and present the occurrence of dose modifying toxicities by cycles and overall
• Anti-epcoritamab antibody response [ Time Frame: throughout the study and up to 2 years following the last patient first dose ]
  calculate incidence of antibody response to epcoritamab in relation to dosing
• Changes in lymphoma symptoms as measured by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) [ Time Frame: throughout the study and up to 2 years following the last patient first dose ]
  monitor change from baseline in health-related quality of life over time and in relation to treatment

Original Secondary Outcome Measures (submitted: November 9, 2020)

• Compare other measures of epcoritamab efficacy to SOC - Progression Free Survival (PFS) [ Time Frame: throughout the study and up to 2 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.
• Compare other measures of epcoritamab efficacy to SOC - Overall Response Rate (ORR) [ Time Frame: throughout the study and up to 2 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.
• Compare other measures of epcoritamab efficacy to SOC - Complete Response (CR) [ Time Frame: throughout the study and up to 2 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.
• Compare other measures of epcoritamab efficacy to SOC - Duration of Response (DOR) [ Time Frame: throughout the study and up to 2 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.
• Compare other measures of epcoritamab efficacy to SOC - Time to Response (TTR) [ Time Frame: throughout the study and up to 2 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.
• Compare other measures of epcoritamab efficacy to SOC - Time to next anti-lymphoma therapy (TTNT) [ Time Frame: throughout the study and up to 2 years following the last patient first dose ]
  TTNT is calculated as the time from randomization to date of initiation of new anti-lymphoma therapy.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Phase 3 Trial of Epcoritamab vs Investigator's Choice Chemotherapy in R/R DLBCL
• Official Title: 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)
• Brief Summary: The drug that will be investigated in the study is an antibody, epcoritamab, also known as 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: 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.
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Diffuse Large B-cell Lymphoma

Intervention

• Biological: Epcoritamab
  Following mandatory pre-medication subject will be administered epcoritamab as a subcutaneous injection.
  Other Name: GEN3013; DuoBody®-CD3xCD20
• Drug: Investigator's Choice Chemotherapy
  Following mandatory pre-medication subject will be administered intravenously either BR or R-GemOx.
  Other Name: BR or R-GemOx

Study Arms

• Experimental: Epcoritamab (GEN3013; DuoBody®CD3xCD20)
  Epcoritamab will be administered in Cycles of 28 days until any of the discontinuation criteria is met
  Intervention: Biological: Epcoritamab
• Active Comparator: Investigator's choice of 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

  Intervention: Drug: Investigator's Choice Chemotherapy

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: November 9, 2020): 480
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: May 2024
• Estimated Primary Completion Date: June 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Main Inclusion Criteria:

1. 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

2. One of the confirmed histologies below with CD20-positivity:

   1. DLBCL, NOS, including de novo or histologically transformed from FL
   2. "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
   3. FL Grade 3B
   4. T-cell/histiocyte-rich large B-cell lymphoma
3. ECOG PS score of 0-2
4. Failed previous HDT-ASCT or not eligible for HDT-ASCT at screening
5. Patients must have detectable disease by PET scan and measurable by CT scan or MRI
6. Acceptable renal and liver function
7. Life expectancy >2 months on SOC treatment

Main Exclusion Criteria:

1. Primary Central Nervous System (CNS) tumor or known CNS involvement
2. Any prior therapy with a bispecific antibody targeting CD3 and CD20
3. Major surgery within 4 weeks prior to randomization
4. Chemotherapy and other non-investigational antineoplastic agents (except CD20 mAbs) within 4 weeks or 5 half-lives (whichever is shorter) prior to randomization
5. Any investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to randomization
6. ASCT within 100 days of randomization
7. Treatment with CAR-T therapy within 100 days prior to randomization
8. Seizure disorder requiring anti-epileptic therapy
9. Clinically significant cardiac disease

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Genmab A/S Trial Information; +45 70202728; clinicaltrials@genmab.com

• Listed Location Countries: Australia, Austria, Belgium, Canada, China, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, Norway, Poland, Russian Federation, Singapore, Spain, Sweden, Taiwan, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT04628494
• Other Study ID Numbers: GCT3013-05; 2020-003016-27 ( EudraCT Number ); jRCT2021220017 ( Registry Identifier: Japan Registry for Clinical Trials (jRCT) ); CTR20221558 ( Registry Identifier: Drug Clinal Trial Registration and Information Disclosure Platform (ChinaDrugTrials.org.cn) ); MOH_2021-01-18_009672 ( Registry Identifier: Clinical Research Site - mytrial )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Genmab
• Original Responsible Party: Same as current
• Current Study Sponsor: Genmab
• Original Study Sponsor: Same as current
• Collaborators: AbbVie
• Investigators: Not Provided
• PRS Account: Genmab
• Verification Date: January 2023