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Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL) (EPCORE™ NHL-2)

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ClinicalTrials.gov Identifier: NCT04663347
Recruitment Status : Recruiting
First Posted : December 11, 2020
Last Update Posted : April 14, 2022
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Genmab

Tracking Information
First Submitted Date  ICMJE October 27, 2020
First Posted Date  ICMJE December 11, 2020
Last Update Posted Date April 14, 2022
Actual Study Start Date  ICMJE November 16, 2020
Estimated Primary Completion Date April 30, 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 1, 2022)
  • Part 1: DLTs [ Time Frame: During the first treatment cycle (28 days) in each cohort ]
    To identify the recommended phase 2 dose (RP2D) and if reached, the Maximum Tolerated Dose (MTD).
  • Part 1 and Part 2: Incidence of adverse events [ Time Frame: From first dose of trial medication to the maximum of 60 days after last dose of epcoritamab or initiation of subsequent anti-lymphoma therapy. ]
    To assess the safety and tolerability of GEN3013 as monotherapy and in combination with other agents.
  • Part 1 and Part 2: Incidence of adverse events [ Time Frame: From first dose of trial medication to the maximum of 30 days after the last dose of any SOC medication or initiation of subsequent anti-lymphoma therapy. ]
    To assess the safety and tolerability of GEN3013 as monotherapy and in combination with other agents.
  • Part 1 and Part 2: Incidence and severity of changes in laboratory values [ Time Frame: From screening until 60 days after last dose, approximately 24 months ]
    Clinical laboratory parameters assessed: hematology, chemistry, coagulation, tumor lysis, immunoglobulins, and urinalyses
  • Part 1 and Part 2: Incidence of dose interruptions and delays [ Time Frame: From first dose until end of treatment, approximately 24 months ]
    Assess the duration of exposure for epcoritamab and combination agents
  • Part 2: Overall Response Rate (ORR) [ Time Frame: From 6 weeks after enrollment until treatment discontinuation, assessed up to 3 years ]
    Assess the preliminary anti-tumor activity of epcoritamab in combination with other agents
Original Primary Outcome Measures  ICMJE
 (submitted: December 4, 2020)
  • Dose Escalation Phase - Number of dose-limiting toxicities (DLTs) [ Time Frame: DLTs are evaluated during the first cycle (28 days) in each cohort ]
    To evaluate the safety of epcoritamab in combination with other agents
  • Dose Escalation Phase - Number of Adverse Events [ Time Frame: From first dose up to safety follow-up (60 days after last trial treatment) ]
    To evaluate the safety of epcoritamab in combination with other agents
  • Expansion Part - Preliminary anti-tumor activity [ Time Frame: Up to approximately 3 years after the last subject's first treatment ]
    To evaluate the overall response rate
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 1, 2022)
  • Total body clearance of drug from the plasma (CL) [ Time Frame: From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years) ]
  • Volume of Distribution [ Time Frame: From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years) ]
  • Area Under the Concentration-Time Curve (AUC) from Time 0 to last quantifiable sample [ Time Frame: From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years) ]
  • Area Under the Concentration-Time Curve (AUC) from Time 0 to infinity [ Time Frame: From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years) ]
  • Maximum observed concentration (Cmax) [ Time Frame: From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years) ]
  • Time to reach Cmax (Tmax) [ Time Frame: From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years) ]
  • Terminal Elimination Half-Life (t 1/2) [ Time Frame: From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years) ]
  • Trough concentrations (Ctrough) [ Time Frame: From first dose and at multiple time points until treatment discontinuation (assessed up to 3 years) ]
  • Incidence of anti-drug antibodies (ADAs) to epcoritamab [ Time Frame: From first dose until end of treatment, approximately 24 months ]
    To evaluate immunogenicity
  • Duration of response (DOR) [ Time Frame: Approximately 3 years after the last subject's first dose ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Time to response (TTR) [ Time Frame: Approximately 3 years after the last subject's first dose ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Progressive-free survival (PFS) [ Time Frame: Approximately 3 years after the last subject's first dose ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Overall survival (OS) [ Time Frame: Approximately 3 years after the last subject's first dose ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Time to next anti-lymphoma therapy (TTNT) [ Time Frame: Approximately 3 years after the last subject's first dose ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Rate of minimal residual disease (MRD) negativity [ Time Frame: Approximately 3 years after the last subject's first dose ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Duration of minimal residual disease (MRD) negativity [ Time Frame: Approximately 3 years after the last subject's first dose ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
Original Secondary Outcome Measures  ICMJE
 (submitted: December 4, 2020)
  • Pharmacokinetics concentration of epcoritamab [ Time Frame: From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years ]
    To evaluate PK parameter - Clearance
  • Pharmacokinetics concentration of epcoritamab [ Time Frame: From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years ]
    To evaluate PK parameter - Volume of distribution
  • Pharmacokinetics concentration of epcoritamab [ Time Frame: From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years ]
    To evaluate PK parameter - AUC0-last (Area under the concentration-time curve (AUC) from time zero to last quantifiable sample)
  • Pharmacokinetics concentration of epcoritamab [ Time Frame: From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years ]
    To evaluate PK parameter - Area under the concentration-time curve (AUC) from time zero to infinity
  • Pharmacokinetics concentration of epcoritamab [ Time Frame: From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years ]
    To evaluate PK parameter - Cmax (maximum (peak) plasma drug concentration)
  • Pharmacokinetics concentration of epcoritamab [ Time Frame: From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years ]
    To evaluatePK parameter - Tmax (time to reach maximum (peak) plasma concentration)
  • Pharmacokinetics concentration of epcoritamab [ Time Frame: From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years ]
    To evaluate PK parameters - Predose values
  • Pharmacokinetics concentration of epcoritamab [ Time Frame: From start of treatment throughout all treatment cycles (each cycle is 28 days) until LPLV, approximately 3 years ]
    To evaluate PK parameters - t½ (elimination half-life)
  • Incidence of anti-drug antibodies (ADAs) to Epcoritamab [ Time Frame: From start of treatment until end of treatment, approximately 24 months ]
    To evaluate immunogenicity
  • Duration of response (DOR) [ Time Frame: Approximately 3 years after the last subject's first treatment ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Time to response (TTR) [ Time Frame: Approximately 3 years after the last subject's first treatment ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Progressive-free survival (PFS) [ Time Frame: Approximately 3 years after the last subject's first treatment ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Overall survival (OS) [ Time Frame: Approximately 3 years after the last subject's first treatment ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Time to next anti-lymphoma therapy (TTNT) [ Time Frame: Approximately 3 years after the last subject's first treatment ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Rate of minimal residual disease (MRD) negativity [ Time Frame: Approximately 3 years after the last subject's first treatment ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Duration of minimal residual disease (MRD) negativity [ Time Frame: Approximately 3 years after the last subject's first treatment ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Safety run-in only: preliminary anti-tumor activity as measured by the overall response rate [ Time Frame: Approximately 3 years after the last subject's first treatment ]
    To evaluate the preliminary anti-tumor activity of epcoritamab in combination with other agents
  • Expansion only: Monitor number and severity of AEs [ Time Frame: Up to safety follow-up (up to 60days after last dose) ]
    To evaluate the safety and tolerability of epcoritamab in combination with other agents
  • Expansion only: Monitor number and severity of changes in laboratory values [ Time Frame: Up to safety follow-up (up to 60days after last dose) ]
    To evaluate the safety and tolerability of epcoritamab in combination with other agents
  • Expansion only: Monitor number of dose interruptions and delays [ Time Frame: Up to safety follow-up (up to 60days after last dose) ]
    To evaluate the safety and tolerability of epcoritamab in combination with other agents
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Trial of Epcoritamab Combinations in Subjects With B-cell Non-Hodgkin Lymphoma (B-NHL)
Official Title  ICMJE 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)
Brief Summary 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 subjects with B-cell Non-Hodgkin Lymphoma (B-NHL).
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 subjects with previously untreated diffuse large B-cell lymphoma (DLBCL)
  • Arm 2: epcoritamab + rituximab and lenalidomide (R2) in subjects with relapsed/refractory (R/R) follicular lymphoma (FL)
  • Arm 3: epcoritamab + rituximab and bendamustine (BR) in subjects with previously untreated FL
  • Arm 4: epcoritamab + rituximab, cytarabine, dexamethasone, and oxaliplatin/ carboplatin (R-DHAX/C) in subjects with R/R DLBCL eligible for autologous stem cell transplant (ASCT)
  • Arm 5: epcoritamab + gemcitabine and oxaliplatin (GemOx) in subjects with R/R DLBCL ineligible for ASCT due to age, performance status (PS), or comorbidity
  • Arm 6: epcoritamab + R2 in subjects with previously untreated FL
  • Arm 7: epcoritamab maintenance in subjects 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 subjects with previously untreated DLBCL who are ineligible to receive full-dose anthracycline

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. Part 2 includes all 8 arms (Arm 1-8) 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 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Diffuse Large B-Cell Lymphoma
  • Follicular Lymphoma
Intervention  ICMJE
  • Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
    21-day cycles
    Other Name: R-CHOP
  • Drug: rituximab and lenalidomide
    28-day cycles
    Other Name: R2
  • Drug: rituximab and bendamustine
    28-day cycles
    Other Name: BR
  • Drug: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
    21-day cycles
    Other Name: R-DHAX/C
  • Drug: gemcitabine and oxaliplatin
    28-day cycles
    Other Name: GemOx
  • Biological: Epcoritamab
    Epcoritamab will be administered in combination with the respective standard of care chemotherapy.
    Other Name: GEN3013; DuoBody®-CD3xCD20
  • Biological: Epcoritamab Maintenance
    28-day cycle for Cycle 1 and then 56-day cycle from Cycle 2 through 13
    Other Name: GEN3013; DuoBody®-CD3xCD20
  • Drug: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
    21-day cycle
    Other Name: R mini-CHOP
Study Arms  ICMJE
  • Experimental: Arm 1 - Epcoritamab + R-CHOP
    In subjects with previously untreated DLBCL
    Interventions:
    • Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
    • Biological: Epcoritamab
  • Experimental: Arm 2 - Epcoritamab + R2
    In subjects with R/R FL
    Interventions:
    • Drug: rituximab and lenalidomide
    • Biological: Epcoritamab
  • Experimental: Arm 3 - Epcoritamab + BR
    In subjects with previously untreated FL
    Interventions:
    • Drug: rituximab and bendamustine
    • Biological: Epcoritamab
  • Experimental: Arm 4 - Epcoritamab + R-DHAX/C
    In subjects with R/R DLBCL Eligible for ASCT
    Interventions:
    • Drug: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
    • Biological: Epcoritamab
  • Experimental: Arm 5 - Epcoritamab + GemOx
    In subjects with R/R DLBCL Ineligible ASCT
    Interventions:
    • Drug: gemcitabine and oxaliplatin
    • Biological: Epcoritamab
  • Experimental: Arm 6 - Epcoritamab + R2
    In subjects with previously untreated FL
    Interventions:
    • Drug: rituximab and lenalidomide
    • Biological: Epcoritamab
  • Experimental: Arm 7 - Epcoritamab maintenance
    In subjects with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L
    Intervention: Biological: Epcoritamab Maintenance
  • Experimental: Arm 8 - Epcoritamab + R mini-CHOP
    In subjects with previously untreated DLBCL who are ineligible to receive full-dose anthracycline
    Interventions:
    • Biological: Epcoritamab
    • Drug: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: April 1, 2022)
396
Original Estimated Enrollment  ICMJE
 (submitted: December 4, 2020)
130
Estimated Study Completion Date  ICMJE November 30, 2024
Estimated Primary Completion Date April 30, 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria

  1. Subject must sign an Informed Consent Form (ICF)
  2. At least 18 years of age
  3. 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)
  4. Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
  5. Acceptable organ function at screening
  6. CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
  7. If of childbearing potential subject must practicing a highly effective method of birth control
  8. 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

Key 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Genmab A/S Trial Information +45 70202728 clinicaltrials@genmab.com
Listed Location Countries  ICMJE Australia,   Belgium,   Czechia,   Denmark,   Finland,   France,   Italy,   Netherlands,   Norway,   Spain,   Sweden,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04663347
Other Study ID Numbers  ICMJE GCT3013-02
2020-000845-15 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Genmab
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Genmab
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE AbbVie
Investigators  ICMJE Not Provided
PRS Account Genmab
Verification Date April 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP