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 |
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Recruitment Status :
Recruiting
First Posted : December 11, 2020
Last Update Posted : February 24, 2023
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Sponsor:
Genmab
Collaborator:
AbbVie
Information provided by (Responsible Party):
Genmab
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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).
| 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 Biological: Epcoritamab Maintenance Drug: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone | Phase 1 Phase 2 |
Expanded Access : An investigational treatment associated with this study is available outside the clinical trial. More info ...
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 : | Interventional (Clinical Trial) |
| Estimated Enrollment : | 396 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 16, 2020 |
| Estimated Primary Completion Date : | April 30, 2023 |
| Estimated Study Completion Date : | November 30, 2024 |
Resource links provided by the National Library of Medicine
MedlinePlus related topics:
Lymphoma
| Arm | Intervention/treatment |
|---|---|
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Experimental: Arm 1 - Epcoritamab + R-CHOP
In subjects with previously untreated DLBCL
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Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
21-day cycles
Other Name: R-CHOP Biological: Epcoritamab Epcoritamab will be administered in combination with the respective standard of care chemotherapy.
Other Name: GEN3013; DuoBody®-CD3xCD20 |
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Experimental: Arm 2 - Epcoritamab + R2
In subjects with R/R FL
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Drug: rituximab and lenalidomide
28-day cycles
Other Name: R2 Biological: Epcoritamab Epcoritamab will be administered in combination with the respective standard of care chemotherapy.
Other Name: GEN3013; DuoBody®-CD3xCD20 |
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Experimental: Arm 3 - Epcoritamab + BR
In subjects with previously untreated FL
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Drug: rituximab and bendamustine
28-day cycles
Other Name: BR Biological: Epcoritamab Epcoritamab will be administered in combination with the respective standard of care chemotherapy.
Other Name: GEN3013; DuoBody®-CD3xCD20 |
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Experimental: Arm 4 - Epcoritamab + R-DHAX/C
In subjects with R/R DLBCL Eligible for ASCT
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Drug: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
21-day cycles
Other Name: R-DHAX/C Biological: Epcoritamab Epcoritamab will be administered in combination with the respective standard of care chemotherapy.
Other Name: GEN3013; DuoBody®-CD3xCD20 |
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Experimental: Arm 5 - Epcoritamab + GemOx
In subjects with R/R DLBCL Ineligible ASCT
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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 |
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Experimental: Arm 6 - Epcoritamab + R2
In subjects with previously untreated FL
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Drug: rituximab and lenalidomide
28-day cycles
Other Name: R2 Biological: Epcoritamab Epcoritamab will be administered in combination with the respective standard of care chemotherapy.
Other Name: GEN3013; DuoBody®-CD3xCD20 |
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Experimental: Arm 7 - Epcoritamab maintenance
In subjects with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L
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Biological: Epcoritamab Maintenance
28-day cycle for Cycle 1 and then 56-day cycle from Cycle 2 through 13
Other Name: GEN3013; DuoBody®-CD3xCD20 |
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Experimental: Arm 8 - Epcoritamab + R mini-CHOP
In subjects with previously untreated DLBCL who are ineligible to receive full-dose anthracycline
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Biological: Epcoritamab
Epcoritamab will be administered in combination with the respective standard of care chemotherapy.
Other Name: GEN3013; DuoBody®-CD3xCD20 Drug: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone 21-day cycle
Other Name: R mini-CHOP |
Primary Outcome Measures :
- 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
Secondary Outcome Measures :
- 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
Information from the National Library of Medicine
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Criteria
Key Inclusion Criteria
- Subject must sign an Informed Consent Form (ICF)
- At least 18 years of age
- 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)
- Eastern Cooperative Oncology Group (ECOG) PS score of 0, 1 or 2
- Acceptable organ function at screening
- CD20-positive non-Hodgkin lymphoma (NHL) at most recent representative tumor biopsy
- If of childbearing potential subject must practicing a highly effective method of birth control
- 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
- Chemotherapy, radiation therapy, or major surgery within 4 weeks prior to the first dose of epcoritamab
- Any prior treatment with a bispecific antibody targeting CD3 and CD20.
- Treatment with CAR-T therapy within 30 days prior to first dose of epcoritamab
- Clinically significant cardiovascular disease
- Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results
- 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
- Active positive tests for hepatitis B virus or hepatitis C virus indicating acute or chronic infection
- Known history of seropositivity of human immunodeficiency virus (HIV)
- Active tuberculosis or history of completed treatment for active tuberculosis within the past 12 months
- Neuropathy > grade 1
- Receiving immunostimulatory agent
- Prior allogeneic HSCT
- 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
| Contact: Genmab A/S Trial Information | +45 70202728 | clinicaltrials@genmab.com |
Locations
Show 64 study locations
Sponsors and Collaborators
Genmab
AbbVie
| Responsible Party: | Genmab |
| ClinicalTrials.gov Identifier: | NCT04663347 |
| Other Study ID Numbers: |
GCT3013-02 2020-000845-15 ( EudraCT Number ) |
| First Posted: | December 11, 2020 Key Record Dates |
| Last Update Posted: | February 24, 2023 |
| Last Verified: | February 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | No |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by Genmab:
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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 Gemcitabine Cytarabine Dexamethasone Prednisone Cyclophosphamide |
Bendamustine Hydrochloride Rituximab Carboplatin Doxorubicin Liposomal doxorubicin Oxaliplatin Vincristine Lenalidomide Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action |