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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04663347
Recruitment Status : Recruiting
First Posted : December 11, 2020
Last Update Posted : May 31, 2024
Sponsor:
Collaborator:
AbbVie
Information provided by (Responsible Party):
Genmab

Brief 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 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.


Condition or disease Intervention/treatment Phase
Diffuse Large B-Cell Lymphoma Follicular Lymphoma Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone Drug: rituximab and lenalidomide Drug: rituximab and bendamustine Drug: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin Drug: gemcitabine and oxaliplatin Biological: Epcoritamab Drug: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone Drug: Lenalidomide Drug: rituximab, ifosfamide, carboplatin, and etoposide phosphate Phase 1 Phase 2

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 662 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : November 3, 2020
Estimated Primary Completion Date : March 31, 2029
Estimated Study Completion Date : March 31, 2029


Arm Intervention/treatment
Experimental: Arm 1 - Epcoritamab + R-CHOP
In participants with previously untreated DLBCL.
Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
21-day cycles
Other Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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™




Primary Outcome Measures :
  1. Part 1: Number of Participants With Dose limiting Toxicities (DLTs) [ Time Frame: During the first cycle (Cycle length= 28 days) in each cohort ]
    DLT events are defined as clinically significant adverse events (AEs) or abnormal laboratory values assessed as unrelated to disease progression, underlying disease, intercurrent illness, or concomitant medications as assessed per Common Terminology Criteria for Adverse Events (NCI-CTCAE) criteria version 5.0.

  2. Part 1 and Part 2 (Arm 7): Number of Participants With Adverse Events (AEs) [ 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. ]
    An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign. (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product.

  3. Part 2 (Except Arm 7): Overall Response Rate (ORR) [ Time Frame: Up to 3 years ]
    ORR is defined as the percentage of participants achieving complete response (CR) or partial response (PR) based on Lugano criteria.


Secondary Outcome Measures :
  1. Part 1 and 2: Clearance (CL) of Epcoritamab [ Time Frame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) ]
  2. Part 1 and 2: Volume of Distribution (Vd) of Epcoritamab [ Time Frame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) ]
  3. Part 1 and 2: Area Under the Concentration-Time Curve (AUC) from Time Zero to Last Quantifiable Dose (AUC0-last) of Epcoritamab [ Time Frame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) ]
  4. Part 1 and 2: Area Under the Concentration-Time Curve (AUC) from Time Zero to Infinity (AUC0-inf) of Epcoritamab [ Time Frame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) ]
  5. Part 1 and 2: Maximum (Peak) Plasma Concentration (Cmax) of Epcoritamab [ Time Frame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) ]
  6. Part 1 and 2: Time to Reach Cmax (Tmax) of Epcoritamab [ Time Frame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) ]
  7. Part 1 and 2: Terminal Elimination Half-Life (t 1/2) of Epcoritamab [ Time Frame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) ]
  8. Part 1 and 2: Plasma Trough (Pre-dose) Concentrations (Ctrough) of Epcoritamab [ Time Frame: Predose and postdose at multiple timepoints until treatment discontinuation (up to 3 years) ]
  9. Part 1 and 2: Number of Immune Cell Populations [ Time Frame: Up to 2 years ]
    Immune cell populations in peripheral blood and tumor biopsies will be assessed.

  10. Part 1 and 2: Percentage of Immune Cell Populations [ Time Frame: Up to 2 years ]
    Immune cell populations in peripheral blood and tumor biopsies will be assessed.

  11. Part 1 and 2: Change From Baseline in Cytokine Levels up to Cycle 3 [ Time Frame: Up to Cycle 3 (cycle length = 21 days for Arms 1, 4, 8 and 10; cycle length = 28 days for Arms 2, 3, 5, 6 and 9; cycle length = 28 days (Cycle 1) and 56 days (Cycles 2, 3) for Arm 7) ]
    Change in cytokine levels in peripheral blood samples will be assessed.

  12. Part 1 and 2: Change From Baseline in Circulating Tumor Deoxyribonucleic Acid (DNA) Level up to End of Treatment (up to 2 Years) [ Time Frame: Up to 2 years ]
    Change in circulating tumor DNA levels will be assessed.

  13. Part 1 and 2: Number of Participants With Anti-Drug Antibodies (ADAs) to Epcoritamab [ Time Frame: Up to 3 years ]
  14. Part 1: ORR [ Time Frame: Up to 3 years ]
    ORR is defined as the percentage of participants achieving CR or PR based on Lugano criteria.

  15. Part 1 and 2: Duration of Response (DOR) [ Time Frame: Up to 3 years ]
    DOR: the time from the first documentation of objective tumor response (CR or PR) to the date of first PD or death based on Lugano criteria.

  16. Part 1 and 2: Time to Response (TTR) [ Time Frame: Up to 3 years ]
    TTR is defined as the time from Day 1 of Cycle 1 to first documentation of objective tumor response (CR or PR).

  17. Part 1 and 2: Progression Free Survival (PFS) [ Time Frame: Up to 3 years ]
    PFS is defined as the time from Day 1 of Cycle 1 to first documented PD or death due to any cause based on Lugano criteria.

  18. Part 1 and 2: Overall Survival (OS) [ Time Frame: Up to 3 years ]
    OS is defined as the time from the date of first dose, to the date of death due to any cause.

  19. Part 1 and 2: Time to Next Anti-lymphoma Therapy (TTNT) [ Time Frame: Up to 3 years ]
    TTNT is defined as the time from Day 1 of Cycle 1 to first documented administration of subsequent anti-lymphoma therapy.

  20. Part 1 and 2: Percentage of Participants With Minimal Residual Disease (MRD) Negativity [ Time Frame: Up to 3 years ]
    It is defined as the percentage of participants with at least 1 MRD negative result.

  21. Part 1 and 2: Duration of minimal residual disease (MRD) negativity [ Time Frame: Up to 3 years ]
  22. Part 2 (Arm 7): Percentage of Participants Who Converted From MRD Positivity to MRD Negativity [ Time Frame: Up to 3 years ]
  23. Part 2 (Except Arm 7): Percentage of Participants with Complete Response (CR) in Arms 1 to 10 [ Time Frame: Up to 3 years ]
  24. Part 2 (Arm 7): Percentage of Participants With CR [ Time Frame: Week 24, Week 48, and Week 96 ]
    It is defined as the percentage of participants who remain in complete remission or converting to complete remission after first trial drug administration.

  25. Part 1 and 2: Time to Complete Response (TTCR) [ Time Frame: Up to 3 years ]
    TTCR is defined as the time from first trial drug administration to the date of first documented complete response post-treatment.

  26. Part 1 and 2: Duration of Complete Response (DoCR) [ Time Frame: Up to 3 years ]
    DoCR is defined as the time from the first documentation of CR to the date of PD or death, whichever occurs first based on Lugano criteria.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key 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

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 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04663347


Contacts
Layout table for location contacts
Contact: Genmab A/S Trial Information +45 70202728 clinicaltrials@genmab.com

Locations
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Sponsors and Collaborators
Genmab
AbbVie
Additional Information:
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Responsible Party: Genmab
ClinicalTrials.gov Identifier: NCT04663347    
Other Study ID Numbers: GCT3013-02
2020-000845-15 ( EudraCT Number )
NL74222.056.20 ( Registry Identifier: CCMO )
283235 ( Other Identifier: IRAS ID; UK Research Summaries Database )
2023-504805-35-00 ( EU Trial (CTIS) Number )
First Posted: December 11, 2020    Key Record Dates
Last Update Posted: May 31, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Genmab:
DuoBody®
monoclonal antibodies
anti-CD3
anti-CD20
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Dexamethasone
Prednisone
Cyclophosphamide
Bendamustine Hydrochloride
Ifosfamide
Rituximab
Carboplatin
Gemcitabine
Doxorubicin
Liposomal doxorubicin
Oxaliplatin
Etoposide
Vincristine
Lenalidomide
Etoposide phosphate
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents