NCT04663347

Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)

A Phase 1b/2, Open-Label Trial to Assess the Safety and Preliminary Efficacy of Epcoritamab (GEN3013; DuoBody®-CD3xCD20) in Combination With Other Agents in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)

• Status: Active Not Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 543 (actual)
• Sponsor: Genmab · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this trial is to measure the safety and effectiveness of epcoritamab (EPKINLY™), either by itself or together with other therapies, when treating participants with B-cell non-Hodgkin Lymphoma (B-NHL). The aim of the first part of the trial is to identify the most appropriate dose of epcoritamab, and the aim of the second part of the trial is to assess the selected epcoritamab dose in a larger group of participants with B-NHL. All participants in this trial will receive either epcoritamab alone, or epcoritamab combined with another standard treatment regimen, with a total of 10 different treatment arms being studied. Trial details include: * The treatment duration for each participant depends upon which arm of treatment they are assigned to. * The visit frequency for each participant depends upon which arm of treatment they are assigned to, but will be weekly to start for all participants, then will decrease to either: every 2 weeks, or every 3 weeks, or every 4 weeks, or every 8 weeks. * All participants will receive active drug; no one will be given placebo. Participants who receive treatment with epcoritamab will have it injected right under the skin. Participants will receive a different regimen of epcoritamab depending upon which arm of treatment they are assigned. Participants who receive standard treatments will have intravenous (IV) infusions and/or oral administration of those treatments. Participants will receive a different standard treatment regimen depending upon which arm of treatment they are assigned.

Detailed description

A Phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab in combination with other standard of care (SOC) agents in participants with B-NHL. All participants in the trial will receive epcoritamab, as monotherapy or in combination. The following regimens will be investigated: * Arm 1: epcoritamab + rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in participants with previously untreated diffuse large B-cell lymphoma (DLBCL) * Arm 2: epcoritamab + rituximab and lenalidomide (R2) in participants with relapsed/refractory (R/R) follicular lymphoma (FL) * Arm 3: epcoritamab + rituximab and bendamustine (BR) in participants with previously untreated FL * Arm 4: epcoritamab + rituximab, cytarabine, dexamethasone, and oxaliplatin/ carboplatin (R-DHAX/C) in participants with R/R DLBCL eligible for autologous stem cell transplant (ASCT) * Arm 5: epcoritamab + gemcitabine and oxaliplatin (GemOx) in participants with R/R DLBCL ineligible for ASCT due to age, performance status (PS), or comorbidity * Arm 6: epcoritamab + R2 in participants with previously untreated FL * Arm 7: epcoritamab maintenance in participants with FL who achieve a complete response (CR) or a partial response (PR) following first or second line SOC treatment * Arm 8: epcoritamab + reduced dose of R-CHOP (R mini-CHOP) in participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline * Arm 9: epcoritamab + lenalidomide for second-line treatment in participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy * Arm 10: epcoritamab + rituximab, ifosfamide, carboplatin, and etoposide phosphate (R-ICE) in participants with R/R DLBCL eligible for ASCT The trial consists of two parts: Part 1 ('Dose Escalation') and Part 2 ('Dose Expansion'). The primary objective of Part 1 is safety, and it includes Arm 1-5 and Arm 10. Part 2 includes all 10 arms (Arm 1-10) and the primary goal of all arms, except Arm 7, is preliminary efficacy. For Arm 7, the primary goal is safety. Participants in Arm 1-5 and Arm 10 can only participate in either Part 1 or Part 2. Dose Limiting Toxicities (DLTs) will be assessed in Part 1 and for a selected number of participants in Arm 8 during a 28-day period (safety run-in). The arms are conducted in parallel.

Conditions

• Diffuse Large B-Cell Lymphoma
• Follicular Lymphoma

Interventions

Type	Name	Description
DRUG	rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone	6 cycles (21-day cycles)
DRUG	rituximab and lenalidomide	rituximab 6 cycles and lenalidomide 12 cycles (28-day cycles)
DRUG	rituximab and bendamustine	6 cycles (28-day cycles)
DRUG	rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin	3 cycles (21-day cycles)
DRUG	gemcitabine and oxaliplatin	4 cycles (28-day cycles)
BIOLOGICAL	Epcoritamab	Every week in cycle 1-4, every 3 weeks in cycle 5 and 6, followed by every 4 weeks in cycle 7 for a total of 1 year.
DRUG	rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone	6 cycles (21-day cycles)
DRUG	Lenalidomide	12 cycles (28-day cycles)
DRUG	rituximab, ifosfamide, carboplatin, and etoposide phosphate	3 cycles (21-day cycles)
BIOLOGICAL	Epcoritamab	Every week in cycle 1-3, every 2 weeks in cycle 4-9, followed by every 4 weeks for a total of 2 years.
BIOLOGICAL	Epcoritamab	Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
BIOLOGICAL	Epcoritamab	Every week in cycle 1 and then every 8 weeks for a total of 2 years.
BIOLOGICAL	Epcoritamab	Every week in cycles 1 and 2, then every 3 weeks in cycles 3 to 6 and then every 4 weeks for cycles 7 and 8.
BIOLOGICAL	Epcoritamab	Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
BIOLOGICAL	Epcoritamab	Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until ASCT or disease progression.
BIOLOGICAL	Epcoritamab	Eligible participants will receive subcutaneous (SC) epcoritamab in 28-day cycles. Fixed-treatment epcoritamab will be administered following a 2-Set Up Dosing regimen in Cycle 1. There will be 2 cohorts, 2a and 2b with different dosing schedules. Cohort 2a will be dosed weekly (QW) in Cycles 1-3, once every 2 weeks (Q2W) in Cycles 4-9, and once every 4 weeks (Q4W) in Cycle 10 and beyond for up to 2 years. In cohort 2b, an alternate dosing schedule for epcoritamab will be explored: epcoritamab administered QW for Cycles 1-2 only, then Q4W in Cycle 3 and beyond for up to 2 years.
DRUG	Rituximab and Lenalidomide	Rituximab 375 milligrams per meter squared (mg/m\^2) will be administered intravenously QW in Cycle 1 and Q4W in Cycles 2-5. Lenalidomide 20 mg will be administered orally daily for 21 days for 12 cycles.
BIOLOGICAL	Epcoritamab	Cycle 1-3 every week, every other week Cycle 4-9 and then Q4W until progression or unacceptable toxicity.

Timeline

• Start date: 2020-11-03
• Primary completion: 2027-09-30
• Completion: 2027-09-30
• First posted: 2020-12-11
• Last updated: 2026-04-08

Locations

57 sites across 13 countries: United States, Australia, Belgium, Czechia, Denmark, Finland, France, Italy, Netherlands, Norway, Spain, Sweden, United Kingdom

Regulatory

• FDA-regulated drug study