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)
Overview
- Phase
- Phase 3
- Intervention
- Epcoritamab
- Conditions
- Diffuse Large B-Cell Lymphoma
- Sponsor
- Genmab
- Enrollment
- 900
- Locations
- 331
- Primary Endpoint
- Number of Participants with Progression-Free Survival (PFS) with an International Prognostic Index (IPI) of 3-5
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
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.
Investigators
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 fresh or paraffin embedded tissue 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.
Arms & Interventions
Epcoritamab and R-CHOP
Participants will receive subcutaneous epcoritamab combined with intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by epcoritamab in 21-day cycles.
Intervention: Epcoritamab
Epcoritamab and R-CHOP
Participants will receive subcutaneous epcoritamab combined with intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by epcoritamab in 21-day cycles.
Intervention: Cyclophosphamide
Epcoritamab and R-CHOP
Participants will receive subcutaneous epcoritamab combined with intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by epcoritamab in 21-day cycles.
Intervention: Rituximab
Epcoritamab and R-CHOP
Participants will receive subcutaneous epcoritamab combined with intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by epcoritamab in 21-day cycles.
Intervention: Vincristine
Epcoritamab and R-CHOP
Participants will receive subcutaneous epcoritamab combined with intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by epcoritamab in 21-day cycles.
Intervention: Doxorubicin
Epcoritamab and R-CHOP
Participants will receive subcutaneous epcoritamab combined with intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by epcoritamab in 21-day cycles.
Intervention: Prednisone
R-CHOP and Rituximab
Participants will receive intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by intravenous rituximab in 21-day cycles.
Intervention: Cyclophosphamide
R-CHOP and Rituximab
Participants will receive intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by intravenous rituximab in 21-day cycles.
Intervention: Rituximab
R-CHOP and Rituximab
Participants will receive intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by intravenous rituximab in 21-day cycles.
Intervention: Vincristine
R-CHOP and Rituximab
Participants will receive intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by intravenous rituximab in 21-day cycles.
Intervention: Doxorubicin
R-CHOP and Rituximab
Participants will receive intravenous rituximab, cyclophosphamide, doxorubixin hydrochloride, vincristine and oral prednisone (R-CHOP) followed by intravenous rituximab in 21-day cycles.
Intervention: Prednisone
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Percentage of Participants with Complete Remission (CR)(On or After to Approximately 28 Weeks)
- Overall survival (OS)(Up to Approximately 76 Months)
- Number of Participants with PFS(Up to Approximately 46 Months)
- Number of Participants with Event-free survival (EFS)(Up to Approximately 46 Months)
- Percentage of Participants with Minimal Residual Disease (MRD) Negativity(Up to Approximately 46 Months)