Purpose

A phase 1b/2, open-label, multinational, interventional trial to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics/biomarkers, immunogenicity, and preliminary efficacy of epcoritamab (EPKINLY™) in combination with other standard of care (SOC) agents in participants with B-cell Non-Hodgkin Lymphoma (B-NHL). The trial consists of 10 different treatment arms. 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 Documented diffuse large B-cell lymphoma (DLBCL) - DLBCL, 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 DLBCL and eligible for HDT-ASCT - DLBCL, NOS - "double-hit" or "triple-hit" DLBCL - FL Grade 3B Arm 5: - Relapsed or refractory documented 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: - DLBCL, NOS - 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 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 30 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. Active 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 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

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 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.