A Study to Evaluate Change in Disease Activity of Subcutaneous (SC) Epcoritamab Combined With Intravenous and Oral Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine, and Prednisone (R-CHOP) or R-CHOP in Adult Participants With Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL) (EPCORE DLBCL-2)

• ClinicalTrials.gov Identifier: NCT05578976
• Recruitment Status: Recruiting
• First Posted: October 13, 2022
• Last Update Posted: May 7, 2024
• Sponsor: Genmab
• Collaborator: AbbVie
• Information provided by (Responsible Party): Genmab

Tracking Information

• First Submitted Date: October 12, 2022
• First Posted Date: October 13, 2022
• Last Update Posted Date: May 7, 2024
• Actual Study Start Date: February 8, 2023
• Estimated Primary Completion Date: January 31, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 28, 2023)

Number of Participants with Progression-Free Survival (PFS) with an International Prognostic Index (IPI) of 3-5 [ Time Frame: Up to Approximately 46 Months ]

PFS is defined as the duration from randomization to the date of disease progression as determined by Lugano 2014 criteria as assessed by Independent Review Committee (IRC), or death due to any cause whichever comes first.

Original Primary Outcome Measures (submitted: October 12, 2022)

Number of Participants with Progression-Free Survival (PFS) [ Time Frame: Up to Approximately 43 Months ]

PFS is defined as the duration from randomization to the date of disease progression as determined by Lugano 2014 criteria as assessed by IRC, or death from any cause.

Current Secondary Outcome Measures (submitted: February 28, 2023)

• Number of Participants with PFS [ Time Frame: Up to Approximately 46 Months ]
  PFS is defined as the duration from randomization to the date of disease progression as determined by Lugano 2014 criteria as assessed by IRC, or death due to any cause, whichever occurs first.
• Number of Participants with Event-free survival (EFS) [ Time Frame: Up to Approximately 46 Months ]
  EFS is defined as the duration from randomization to the date of disease progression determined by Lugano criteria as assessed by IRC, IRC-assessed PR or SD followed by non protocol-specified NALT, a positive biopsy on or after end-of-treatment (EOT), regardless of whether NAL initiated, or death from any cause.
• Percentage of Participants with Complete Remission (CR) [ Time Frame: On or After to Approximately 28 Weeks ]
  CR is defined as the absence of lymphoma determined by fluorodeoxyglucose positron emission tomography (FDG-PET),determined by Lugano 2014 criteria as assessed by IRC.
• Overall survival (OS) [ Time Frame: Up to Approximately 76 Months ]
  OS is defined as time from randomization until death due to any causes.
• Percentage of Participants with Minimal Residual Disease (MRD) Negativity [ Time Frame: Up to Approximately 46 Months ]
  The MRD negativity rate is defined as the percentage of participants who achieve MRD negativity prior to the initiation of any non-protocol-specified new anti-lymphoma therapy.

Original Secondary Outcome Measures (submitted: October 12, 2022)

• Number of Participants with Event-free survival (EFS) [ Time Frame: Up to Approximately 43 Months ]
  EFS is defined as the duration from randomization to the date of disease progression determined by Lugano 2014 criteria as assessed by IRC, Initiation of any non-protocol-specified new anti-lymphoma therapy for any reason, or death from any cause.
• Percentage of Participants with Complete Remission (CR) [ Time Frame: Up to Approximately 28 Weeks ]
  CR is defined as the absence of lymphoma determined by fluorodeoxyglucose positron emission tomography (FDG-PET),determined by Lugano 2014 criteria as assessed by IRC.
• Overall survival (OS) [ Time Frame: Up to Approximately 73 Months ]
  OS is defined as time from randomization until death due to any causes.
• Percentage of Participants with Minimal Residual Disease (MRD) Negativity [ Time Frame: Up to Approximately 73 Months ]
  The MRD negativity rate is defined as the percentage of participants who achieve MRD negativity prior to the initiation of any non-protocol-specified 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 Study to Evaluate Change in Disease Activity of Subcutaneous (SC) Epcoritamab Combined With Intravenous and Oral Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine, and Prednisone (R-CHOP) or R-CHOP in Adult Participants With Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL)
• Official Title: A Phase 3, Randomized, Open-Label Study to Evaluate Safety and Efficacy of Epcoritamab in Combination With R-CHOP Compared to R-CHOP in Subjects With Newly Diagnosed Diffuse Large B-Cell Lymphoma (DLBCL)

Brief Summary

B-cell Lymphoma is an aggressive and rare cancer of a type of immune cells (a white blood cell responsible for fighting infections). The purpose of this study is to assess the change in disease activity of epcoritamab when combined with intravenous and oral rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) or R-CHOP in adult participants globally with diffuse large b-cell lymphoma (DLBCL). Change in disease activity will be assessed.

Epcoritamab is an investigational drug being developed for the treatment of DLBCL. Study doctors put the participants in groups called treatment arms. Participants will receive epcoritamab combined with R-CHOP, followed by epcoritamab or R-CHOP followed by rituximab will be explored. Approximately 900 adult participants with with newly diagnosed DLBCL will be enrolled in the study in approximately 315 sites in globally.

In the Arm 1, participants will receive subcutaneous epcoritamab combined with intravenous and oral R-CHOP followed by subcutaneous epcoritamab in 21-day cycles. In the Arm 2, participants will receive intravenous and oral R-CHOP followed by intravenous rituximab in 21-day cycles.

There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at an approved institution (hospital or clinic). The effect of the treatment will be frequently checked by medical assessments, blood tests, questionnaires and side effects.

• Detailed Description: Not Provided
• 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

• Drug: Epcoritamab
  Subcutaneous Injection (SC)
  Other Name: ABBV-GMAB-3013
• Drug: Cyclophosphamide
  Intravenous (IV) Injection
• Drug: Rituximab
  IV Infusion
• Drug: Vincristine
  IV Infusion
• Drug: Doxorubicin
  IV Infusion
• Drug: Prednisone
  Oral; Tablet

Study Arms

• Experimental: Epcoritamab and R-CHOP
  Participants will receive subcutaneous epcoritamab combined with intravenous and oral rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) followed by epcoritamab in 21-day cycles.
  Interventions:

  • Drug: Epcoritamab
  • Drug: Cyclophosphamide
  • Drug: Rituximab
  • Drug: Vincristine
  • Drug: Doxorubicin
  • Drug: Prednisone
• Experimental: R-CHOP and Rituximab
  Participants will receive intravenous and oral R-CHOP followed by intravenous rituximab in 21-day cycles.
  Interventions:

  • Drug: Cyclophosphamide
  • Drug: Rituximab
  • Drug: Vincristine
  • Drug: Doxorubicin
  • Drug: Prednisone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: October 12, 2022): 900
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 30, 2029
• Estimated Primary Completion Date: January 31, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Planned to receive treatment with 6 cycles of standard rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R-CHOP) per investigator determination.

• Must have newly diagnosed, histologically confirmed CD20+ diffuse large b-cell lymphoma [DLBCL] (de novo or histologically transformed from a diagnosis of follicular lymphoma) at most recent representative tumor biopsy based on the pathology report, with a World Health Organization (WHO) 2016 classification and including:

  • DLBCL, Not Otherwise Specified (NOS).
  • High grade B-cell lymphoma with MYC and BCL-2 and/or BCL-6 rearrangement with DLBCL morphology.
  • T-cell/histiocyte-rich large B-cell lymphoma.
  • Epstein Barr virus-positive DLBCL, NOS.
  • Follicular lymphoma Grade 3b.

Note: The local pathology report must be available at Screening to support CD20+ DLBCL histology.

Composite/intermediate histology with any of the following components is not allowed: high grade B-cell lymphoma, NOS; Hodgkin's lymphoma; primary mediastinal (thymic) large B-cell lymphoma; Burkitt; plasmablastic lymphoma or any CD20- lymphoma, such as anaplastic lymphoma kinase-positive large B-cell lymphoma, human herpesvirus type 8-positive DLBCL, or primary effusion lymphoma.

• Availability of archival or freshly collected tumor tissue at Screening. Archival paraffin-embedded tissue must be obtained within 8 weeks prior to Cycle 1 Day 1.
• Must have an IPI score of 2-5. The number of participants with IPI 2 will not exceed approximately 30% of the overall sample size.
• Must have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2 prior to initiating R-CHOP treatment. Note that participant with an initial ECOG performance status >= 3 may be screened if pre-phase treatment is planned. Participant may be eligible if ECOG performance status were to improve to 0-2 during pre-phase treatment.

• Has at least one target lesion defined as:

  • >= 1 measurable nodal lesion (long axis > 1.5 cm ) or >= 1 measurable extra-nodal lesion (long axis > 1 cm) on computed tomography (CT) scan or magnetic resonance imaging (MRI). AND
  • Positron emission tomography (PET)-positive on PET-CT scan.
• Laboratory values meeting the criteria laid out in the protocol.
• Left ventricular ejection fraction must be >= 50% by multi-gated acquisition or transthoracic echocardiography at Screening.

Exclusion Criteria:

• History of prior systemic anti-lymphoma therapy for diagnosed diffuse large b-cell lymphoma (DLBCL) including any definitive radiotherapy with curative intent] other than corticosteroids with or without vincristine during prephase treatment, or non-curative intent palliative radiotherapy with the stipulation that radiated lesions cannot be selected as target lesion for response assessment.
• Clinically significant cardiovascular disease as per the protocol.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 79 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: ABBVIE CALL CENTER; 844-663-3742; abbvieclinicaltrials@abbvie.com

• Listed Location Countries: Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czechia, Denmark, France, Greece, Hungary, Israel, Italy, Japan, Korea, Republic of, Netherlands, New Zealand, Poland, Portugal, Puerto Rico, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, United Kingdom, United States
• Removed Location Countries: Argentina, Germany, Mexico

Administrative Information

• NCT Number: NCT05578976
• Other Study ID Numbers: M20-621; 2021-000168-31 ( EudraCT Number )
• 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
• Product Manufactured in and Exported from the U.S.: Yes

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Clinical Study Report (CSR)
• Time Frame: For details on when studies are available for sharing visit https://vivli.org/ourmember/abbvie/
• Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous independent scientific research, and will be provided following review and approval of a research proposal and statistical analysis plan and execution of a data sharing statement. Data requests can be submitted at any time after approval in the US and/or EU and a primary manuscript is accepted for publication. For more information on the process, or to submit a request, visit the following link https://www.abbvieclinicaltrials.com/hcp/data-sharing/
• URL: https://vivli.org/ourmember/abbvie/

• Current Responsible Party: Genmab
• Original Responsible Party: AbbVie
• Current Study Sponsor: Genmab
• Original Study Sponsor: AbbVie
• Collaborators: AbbVie

Investigators

• Study Director: ABBVIE INC.; AbbVie

• PRS Account: Genmab
• Verification Date: May 2024