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.
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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
78
Epcoritamab will be administered subcutaneously in cycles of 4 weeks (i.e. 28 days)
Epcoritamab will be administered in combination with the respective SOC chemotherapy followed by epcoritamab monotherapy.
28-day cycles
28-day cycle for Cycle 1 and then 56-day cycle from Cycle 2 through 13
28-day cycles.
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
...and 5 more locations
Part 1: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
Time frame: 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)
Time frame: DLTs are assessed during the first cycle (28 days) in each cohort
Part 2, Arm 1: Objective Response Rate (ORR)
Time frame: Up to 1.5 years
Part 2, Arms 2-4: Number of Participants with DLTs
Time frame: DLTs are assessed during the first cycle (28 days) in arms 2-4
Part 2, Arms 2-5: Number of Participants with TEAEs
Time frame: From first dose until the end of the safety follow-up period (60 days after last dose), up to approximately 5 years
Both parts: Area-under-the-concentration-time curve from Time 0 to Time of last dose (AUClast)
Time frame: From first dose until treatment discontinuation, expected average of 1 year
Both parts: AUC from Time 0 to Infinity (AUCinf)
Time frame: From first dose until treatment discontinuation, expected average of 1 year
Both parts: Maximum (Peak) Plasma Concentration (Cmax)
Time frame: From first dose until treatment discontinuation, expected average of 1 year
Both parts: Time to Reach Cmax (Tmax)
Time frame: From first dose until treatment discontinuation, expected average of 1 year
Both parts: Pre-dose (Trough) Concentrations (Cthrough)
Time frame: From first dose until treatment discontinuation, expected average of 1 year
Both parts: Total Body Clearance of Drug from the Plasma (CL)
Time frame: From first dose until treatment discontinuation, expected average of 1 year
Both parts: Volume of Distribution (Vd)
Time frame: From first dose until treatment discontinuation, expected average of 1 year
Both parts: Elimination Half-life (t 1/2)
Time frame: From first dose until treatment discontinuation, expected average of 1 year
Both parts: Number of Participants with Anti-Drug-Antibodies (ADAs)
Time frame: From first dose until treatment discontinuation, expected average of 1 year
Part 2, Arm 1: Number of Participants with TEAEs
Time frame: 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
Time frame: Up to 1.5 years
Both parts: CR Rate
Time frame: Up to 1.5 years
Both parts: Duration of Response (DOR)
Time frame: Up to 1.5 years
Both parts: Progression Free Survival (PFS)
Time frame: Up to 1.5 years
Part 2: Duration of CR (DoCR)
Time frame: Up to 1.5 years
Part 2: Time to Response (TTR)
Time frame: Up to 1.5 years
Part 1 and Part 2 arm 1: Time to Next Anti-lymphoma Therapy (TTNT)
Time frame: Up to 1.5 years
Both parts: Overall Survival (OS)
Time frame: Up to 1.5 years
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