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

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Genmab

Status and phase

Enrolling
Phase 2
Phase 1

Conditions

Follicular Lymphoma
Diffuse Large B-Cell Lymphoma

Treatments

Drug: rituximab and lenalidomide
Drug: gemcitabine and oxaliplatin
Drug: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
Drug: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
Drug: rituximab and bendamustine
Drug: Lenalidomide
Drug: rituximab, ifosfamide, carboplatin, and etoposide phosphate
Biological: Epcoritamab
Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone

Study type

Interventional

Funder types

Industry

Identifiers

NCT04663347
2020-000845-15 (EudraCT Number)
2023-504805-35-00 (Registry Identifier)
283235 (Other Identifier)
GCT3013-02
NL74222.056.20 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

662 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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 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 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.

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

662 participants in 10 patient groups

Arm 1 - Epcoritamab + R-CHOP
Experimental group
Description:
In participants with previously untreated DLBCL.
Treatment:
Drug: rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone
Biological: Epcoritamab
Arm 2 - Epcoritamab + R2
Experimental group
Description:
In participants with R/R FL.
Treatment:
Biological: Epcoritamab
Drug: rituximab and lenalidomide
Arm 3 - Epcoritamab + BR
Experimental group
Description:
In participants with previously untreated FL.
Treatment:
Biological: Epcoritamab
Drug: rituximab and bendamustine
Arm 4 - Epcoritamab + R-DHAX/C
Experimental group
Description:
In participants with R/R DLBCL eligible for ASCT.
Treatment:
Biological: Epcoritamab
Drug: rituximab, cytarabine, dexamethasone, and oxaliplatin/carboplatin
Arm 5 - Epcoritamab + GemOx
Experimental group
Description:
In participants with R/R DLBCL ineligible ASCT.
Treatment:
Biological: Epcoritamab
Drug: gemcitabine and oxaliplatin
Arm 6 - Epcoritamab + R2
Experimental group
Description:
In participants with previously untreated FL.
Treatment:
Biological: Epcoritamab
Drug: rituximab and lenalidomide
Arm 7 - Epcoritamab maintenance
Experimental group
Description:
In participants with FL who achieved a CR or PR after receiving SOC treatment in 1L or 2L.
Treatment:
Biological: Epcoritamab
Arm 8 - Epcoritamab + R mini-CHOP
Experimental group
Description:
In participants with previously untreated DLBCL who are ineligible to receive full-dose anthracycline.
Treatment:
Biological: Epcoritamab
Drug: rituximab, cyclophosphamide, reduced dose of doxorubicin, vincristine, and prednisone
Arm 9 - Epcoritamab + Lenalidomide
Experimental group
Description:
In participants with FL who progressed within 24 months of initiation of first-line anti-CD20-containing immunochemotherapy.
Treatment:
Biological: Epcoritamab
Drug: Lenalidomide
Arm 10 - Epcoritamab + R-ICE
Experimental group
Description:
In participants with R/R DLBCL eligible for ASCT.
Treatment:
Biological: Epcoritamab
Drug: rituximab, ifosfamide, carboplatin, and etoposide phosphate

Trial contacts and locations

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Central trial contact

Genmab A/S Trial Information

Data sourced from clinicaltrials.gov

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