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Purpose

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 subjects 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 total trial duration will be up to 6 years. - The treatment duration for each participant depends upon which arm of treatment they are assigned to receive, but will be no more than 3 years. - The visit frequency for each participant depends upon which arm of treatment they are assigned to receive, 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 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. Arm 9 (follicular lymphoma (FL)) is still open for enrolment of new patients, while the other arms have closed their recruitment.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  1. Measurable disease defined as ≥1 measurable nodal lesion (long axis >1.5 cm and short axis >1.0 cm) or ≥1 measurable extra-nodal lesion (long axis >1.0 cm) on computed tomography (CT) or magnetic resonance imaging (MRI) 2. Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2 3. Acceptable organ function at screening 4. CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy 5. If of childbearing potential subject must practicing a highly effective method of birth control 6. A man who is sexually active with a woman of childbearing potential must agree to use a barrier method of birth control Arm 1: - Newly diagnosed DLBCL - DLBCL, not otherwise specified (NOS) - "Double-hit" or "triple-hit" DLBCL - FL Grade 3B Arm 2: R/R FL Arm 3: Newly diagnosed, previously untreated FL grade 1-3A Arm 4: - Documented R/R DLBCL and eligible for HDT-ASCT - DLBCL, NOS - "Double-hit" or "triple-hit" DLBCL - FL Grade 3B Arm 5: - Documented R/R DLBCL and ineligible for HDT-ASCT - DLBCL, NOS - "Double-hit" or "triple-hit" DLBCL - FL Grade 3B Arm 6: Newly diagnosed, previously untreated FL grade 1-3A Arm 7: - FL Grade 1-3A - If PR or CR per Lugano criteria following first-line or second-line treatment with SOC regimen, and last dose of SOC within 6 months prior to enrollment. Arm 8: - Newly diagnosed DLBCL who are not fit to receive full-dose anthracycline - T-cell/histiocyte rich DLBCL - "Double-hit" or "triple-hit" DLBCL - FL Grade 3B Arm 9: - R/R FL - Progressed within 24 months of initiating first-line treatment Arm 10: - Documented R/R DLBCL and eligible for HDT-ASCT - DLBCL, NOS - "Double-hit" or "triple-hit" DLBCL - FL Grade 3B

Exclusion Criteria

  1. Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab 2. Any prior treatment with a bispecific antibody targeting CD3 and CD20. 3. Treatment with CAR-T therapy within 100 days prior to first dose of epcoritamab 4. Clinically significant cardiovascular disease 5. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results 6. CNS lymphoma or known CNS involvement by lymphoma at screening as confirmed by MRI/CT scan of the brain and, if clinically indicated, by lumbar puncture 7. Positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection 8. Known history of seropositivity of human immunodeficiency virus (HIV) 9. Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months 10. Neuropathy > grade 1 11. Receiving immunostimulatory agent 12. Prior allogeneic HSCT 13. Current seizure disorder requiring anti-epileptic therapy NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Arm 1 - Epcoritamab + R-CHOP 		In participants with previously untreated DLBCL.
  • Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
    21-day cycles
    Other names:
    • R-CHOP
  • 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.
    Other names:
    • GEN3013
    • DuoBody®-CD3xCD20
    • EPKINLY™
Experimental
Arm 2 - Epcoritamab + R2 		In participants with R/R FL.
  • Drug: rituximab and lenalidomide
    28-day cycles
    Other names:
    • R2
  • 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.
    Other names:
    • GEN3013
    • DuoBody®-CD3xCD20
    • EPKINLY™
Experimental
Arm 3 - Epcoritamab + BR 		In participants with previously untreated FL.
  • Drug: rituximab and bendamustine
    28-day cycles
    Other names:
    • BR
  • 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.
    Other names:
    • GEN3013
    • DuoBody®-CD3xCD20
    • EPKINLY™
Experimental
Arm 4 - Epcoritamab + R-DHAX/C 		In participants with R/R DLBCL eligible for ASCT.
  • Drug: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
    21-day cycles
    Other names:
    • R-DHAX/C
  • Biological: Epcoritamab
    Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until disease progression or unacceptable toxicity.
    Other names:
    • GEN3013
    • DuoBody®-CD3xCD20
    • EPKINLY™
Experimental
Arm 5 - Epcoritamab + GemOx 		In participants with R/R DLBCL ineligible ASCT.
  • Drug: gemcitabine and oxaliplatin
    28-day cycles
    Other names:
    • GemOx
  • Biological: Epcoritamab
    Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until disease progression or unacceptable toxicity.
    Other names:
    • GEN3013
    • DuoBody®-CD3xCD20
    • EPKINLY™
Experimental
Arm 6 - Epcoritamab + R2 		In participants with previously untreated FL.
  • Drug: rituximab and lenalidomide
    28-day cycles
    Other names:
    • R2
  • Biological: Epcoritamab
    Every week in cycle 1 and 2, followed by every 4 weeks for a total of 2 years.
    Other names:
    • GEN3013
    • DuoBody®-CD3xCD20
    • EPKINLY™
Experimental
Arm 7 - Epcoritamab maintenance 		In participants with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L.
  • Biological: Epcoritamab
    Every week in cycle 1 and then every 8 weeks for a total of 2 years.
    Other names:
    • GEN3013
    • DuoBody®-CD3xCD20
    • EPKINLY™
Experimental
Arm 8 - Epcoritamab + R mini-CHOP 		In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline.
  • Drug: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
    21-day cycles
    Other names:
    • R mini-CHOP
  • 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.
    Other names:
    • GEN3013
    • DuoBody®-CD3xCD20
    • EPKINLY™
Experimental
Arm 9 - Epcoritamab + Lenalidomide 		In participants with R/R FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy.
  • Drug: Lenalidomide
    28-day cycles
  • Biological: Epcoritamab
    Every week in cycle 1-3 and then every 4 weeks for a total of 2 years.
    Other names:
    • GEN3013
    • DuoBody®-CD3xCD20
    • EPKINLY™
Experimental
Arm 10 - Epcoritamab + R-ICE 		In participants with R/R DLBCL eligible for ASCT.
  • Drug: rituximab, ifosfamide, carboplatin, and etoposide phosphate
    21-day cycles
    Other names:
    • R-ICE
  • Biological: Epcoritamab
    Every week in cycle 1-4, every 2 weeks in cycle 5-9 followed by every 4 weeks until transplant or disease progression.
    Other names:
    • GEN3013
    • DuoBody®-CD3xCD20
    • EPKINLY™

Recruiting Locations

University of Alabama at Birmingham
Birmingham, Alabama 35294

More Details

Status
Recruiting
Sponsor
Genmab

Study Contact

Genmab A/S Trial Information
+45 70202728
clinicaltrials@genmab.com

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) 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) with 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. Patients 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 patients in Arm 8 during a 28-day period ('safety-run phase'). The arms are conducted in parallel.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.