Trial of the Safety and Efficacy of Epcoritamab in Japanese Subjects With Relapsed or Refractory (R/R) B-Cell Non-Hodgkin Lymphoma (R/R B-NHL)
- Conditions
- Diffuse Large B Cell LymphomaPrimary Mediastinal Large B Cell LymphomaHigh-grade B-cell LymphomaFollicular LymphomaSmall Lymphocytic LymphomaMarginal Zone Lymphoma
- Interventions
- Registration Number
- NCT04542824
- Lead Sponsor
- Genmab
- 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
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 78
• Must be at least 20 years of age, inclusive
• Japanese participants
• CD20 positivity at representative tumor biopsy
-
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
-
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
• 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)
Exclusion criteria for Part 2, Arms 2 through 5:
Arm 2:
• FL Grade 3b
• Histologic evidence of transformation to an aggressive lymphoma
- Contraindication to rituximab or lenalidomide
- Unwilling or unable to take aspirin prophylaxis or prophylactic anticoagulant as clinically indicated
Arm 3:
• Contraindication to any of the individual drugs of the R-CHOP regimen
Arm 4:
- Contraindication to any of the individual drugs of the GemOx regimen
Arm 5:
- FL Grade 3b
- Histologic evidence of transformation to an aggressive lymphoma
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm 1: Epcoritamab Epcoritamab (monotherapy) In participants with DLBCL/FL. Arm 2: Epcoritamab + Rituximab + Lenalidomide Epcoritamab In participants with R/R FL Arm 2: Epcoritamab + Rituximab + Lenalidomide Rituximab and lenalidomide In participants with R/R FL Arm 3: Epcoritamab + Rituximab + Cyclophosphamide+ Doxorubicin+ Vincristine + Prednisone Epcoritamab In participants with previously untreated DLBCL Arm 3: Epcoritamab + Rituximab + Cyclophosphamide+ Doxorubicin+ Vincristine + Prednisone Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone In participants with previously untreated DLBCL Arm 4: Epcoritamab + Gemcitabine + Oxaliplatin Epcoritamab In participants with relapsed/refractory DLBCL Arm 4: Epcoritamab + Gemcitabine + Oxaliplatin Gemcitabine and oxaliplatin In participants with relapsed/refractory DLBCL Arm 5: Epcoritamab Maintenance Epcoritamab (maintenance) In participants with FL in CR or in PR following 1L or 2L SOC treatment
- Primary Outcome Measures
Name Time Method 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 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
- Secondary Outcome Measures
Name Time Method Both parts: CR Rate Up to 1.5 years 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: 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: Time to Reach Cmax (Tmax) 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: 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
Trial Locations
- Locations (15)
Tohoku University Hoaspital
🇯🇵Sendai, Miyagi, Japan
Aichi Cancer Center Hospital
🇯🇵Aichi, Japan
NHO Nagoya Medical Center
🇯🇵Aichi, Japan
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Matsuyama Red Cross Hospital
🇯🇵Ehime, Japan
National Hospital Organization Kyushu Cancer Center
🇯🇵Fukuoka, Japan
Fukushima Medical University Hospital
🇯🇵Fukushima, Japan
Kagoshima University Hospital
🇯🇵Kagoshima, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
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