Diffuse Large B Cell Lymphoma, Follicular Lymphoma, High-grade B-cell Lymphoma, Marginal Zone Lymphoma, Primary Mediastinal Large B Cell Lymphoma, Small Lymphocytic Lymphoma
Conditions
Brief summary
The trial is an open-label, multi-center safety and preliminary efficacy trial of epcoritamab (EPKINLY™) in Japanese participants with relapsed, progressive or refractory B-cell lymphomas and Japanese participants with B-cell lymphomas that have achieved partial response (PR) or complete response (CR) following prior standard of care (SOC). The trial consists of two parts: Part 1, dose escalation (phase 1), and Part 2, expansion (phase 2). The purpose of the dose-escalation part of the trial is to determine the maximum tolerated dose (MTD) and the recommended Phase-2 dose (RP2D), as well as to establish the safety profile of epcoritamab in Japanese participants with relapsed, progressive or refractory B-cell lymphoma and Japanese participants with B-cell lymphomas that have achieved PR or CR. In the expansion part, additional participants will be treated with epcoritamab, at the RP2D and the purpose is to further explore and determine the safety and efficacy of epcoritamab. Part 2 of the trial will be initiated once the RP2D has been determined in Part 1. In Part 2, epcoritamab is investigated as a monotherapy and in combination with other SOC agents.
Detailed description
All participants in the trial will receive epcoritamab, as monotherapy or in combination with SOC. The following regimens will be investigated in Part 2: Arm 1: epcoritamab monotherapy in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) Arm 2: epcoritamab + rituximab and lenalidomide (R2) in participants with R/R FL Arm 3: epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in participants with previously untreated DLBCL with high risk features Arm 4: epcoritamab + gemcitabine and oxaliplatin (GemOx) in participants with R/R DLBCL who either failed prior autologous hematopoietic stem cell transplantation (ASCT), or are ineligible for autologous HSCT. Arm 5: epcoritamab maintenance in participants with FL who achieve a CR or a PR following first line (1L)/second line (2L) SOC treatment
Interventions
BIOLOGICALEpcoritamab (monotherapy)
Epcoritamab will be administered subcutaneously in cycles of 4 weeks (i.e. 28 days)
BIOLOGICALEpcoritamab
Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.
28-day cycles
BIOLOGICALEpcoritamab (maintenance)
28-day cycle for Cycle 1 and then 56-day cycle from Cycle 2 through 13
28-day cycles.
Sponsors
Genmab
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1: Sequential Assignment Part 2: Parallel Group Assignment
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: • Must be at least 20 years of age, inclusive • Japanese participants • CD20 positivity at representative tumor biopsy 1. Part 1: * Diffuse large B-cell lymphoma (de novo or histologically transformed) * High-grade B-cell lymphoma * Primary mediastinal large B-cell lymphoma * Follicular lymphoma * Marginal zone lymphoma (nodal, extranodal of mucosa-associated lymphoid tissue, or splenic) * Small lymphocytic lymphoma 2. Part 2 : Arm 1: * Diffuse large B-cell lymphoma (de novo or histologically transformed) * Follicular lymphoma grade 1-3A * Relapsed or refractory disease and previously treated with at least 2 lines of systemic antineoplastic therapy including at least 1 anti-CD20 monoclonal antibody (mAb)-containing therapy. * Measurable disease by computed tomography (CT), magnetic resonance imaging (MRI) or positron emission tomography (PET)-CT scan Arm 2: • R/R FL grade 1, 2 or 3a, stage II, III, or IV, without evidence of transformation. * Previously treated with at least 1 prior anti-neoplastic agent, including anti-CD20 antibody * Must have a need for treatment initiation based on symptoms and/or disease burden (Groupe d'Etude des Lymphomes Folliculaires \[GELF\] criteria) * Eligible to receive R2 per investigator determination Arm 3: * One of following confirmed histologies (de novo or histologically transformed from FL or nodal marginal zone lymphoma) : o DLBCL, not otherwise specified (NOS) * "Double-hit" or "triple-hit" DLBCL * FL Grade 3B. * T-cell/histiocyte rich large B-cell lymphoma (LBCL) * International Prognostic Index (IPI) score ≥3 * No prior therapy for DLBCL or FL grade 3B (G3B) other than nodal biopsy, corticosteroids, or palliative radiotherapy. * Eligible to receive R-CHOP per investigator determination Arm 4: * One of following confirmed histologies (de novo or histologically transformed from FL or nodal marginal zone lymphoma) including: o DLBCL, NOS. o "Double-hit" or "triple-hit" DLBCL * FL Grade 3B. * T-cell/histiocyte rich LBCL * Relapsed or refractory to at least one prior therapy including at least one prior anti-CD20 antibody. * Either failed prior autologous hematopoietic stem cell transplantation (ASCT), or ineligible for autologous hematopoietic stem-cell transplantation (HSCT) * Eligible to receive GemOx per investigator determination Arm 5: • History of histologically confirmed CD20+ FL Grade 1-3a without evidence of transformation. • In CR or PR per Lugano criteria following first-line or second-line treatment with SOC regimen, including anti-CD20 antibody, and last dose of SOC within 6 months prior to enrollment Main
Exclusion criteria
• Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening • Participants not eligible for high dose therapy with autologous hematopoietic stem cell transplantation due to personal choice, social issues, or similar • Known clinically significant cardiac disease • Chronic ongoing infectious diseases requiring treatment (excluding prophylactic treatment)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Part 2, Arms 2-5: Number of Participants with TEAEs | From first dose until the end of the safety follow-up period (60 days after last dose), up to approximately 5 years |
| Part 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs) | From first dose until the end of the safety follow-up period (60 days after last dose), up to approximately 5 years |
| Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) | DLTs are assessed during the first cycle (28 days) in each cohort |
| Part 2, Arm 1: Objective Response Rate (ORR) | Up to 1.5 years |
| Part 2, Arms 2-4: Number of Participants with DLTs | DLTs are assessed during the first cycle (28 days) in arms 2-4 |
Secondary
| Measure | Time frame |
|---|---|
| Part 2, Arm 1: Number of Participants with TEAEs | From first dose until the end of the safety follow-up period (60 days after last dose), up to approximately 5 years |
| Part 1 and Part 2, Arms 2-5: ORR | Up to 1.5 years |
| Both parts: CR Rate | Up to 1.5 years |
| Both parts: Duration of Response (DOR) | Up to 1.5 years |
| Both parts: Progression Free Survival (PFS) | Up to 1.5 years |
| Part 2: Duration of CR (DoCR) | Up to 1.5 years |
| Part 2: Time to Response (TTR) | Up to 1.5 years |
| Part 1 and Part 2 arm 1: Time to Next Anti-lymphoma Therapy (TTNT) | Up to 1.5 years |
| Both parts: Overall Survival (OS) | Up to 1.5 years |
| Both parts: Area-under-the-concentration-time curve from Time 0 to Time of last dose (AUClast) | From first dose until treatment discontinuation, expected average of 1 year |
| Both parts: AUC from Time 0 to Infinity (AUCinf) | From first dose until treatment discontinuation, expected average of 1 year |
| Both parts: Maximum (Peak) Plasma Concentration (Cmax) | From first dose until treatment discontinuation, expected average of 1 year |
| Both parts: Pre-dose (Trough) Concentrations (Cthrough) | From first dose until treatment discontinuation, expected average of 1 year |
| Both parts: Time to Reach Cmax (Tmax) | From first dose until treatment discontinuation, expected average of 1 year |
| Both parts: Total Body Clearance of Drug from the Plasma (CL) | From first dose until treatment discontinuation, expected average of 1 year |
| Both parts: Volume of Distribution (Vd) | From first dose until treatment discontinuation, expected average of 1 year |
| Both parts: Elimination Half-life (t 1/2) | From first dose until treatment discontinuation, expected average of 1 year |
| Both parts: Number of Participants with Anti-Drug-Antibodies (ADAs) | From first dose until treatment discontinuation, expected average of 1 year |
Countries
Japan
Outcome results
None listed