Safety and Efficacy of Epcoritamab With Gemcitabine, Dexamethasone, and Cisplatin (GDP) Salvage Chemotherapy in Relapsed Refractory Large B-cell Lymphoma

NCT ID: NCT05852717

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-10-31
• Study Completion Date: 2028-11-30

Brief Summary

Subjects with relapsed large cell lymphoma will receive 3 cycles of combination therapy consisting of GDP and epcoritamab. Each cycle will last 21 days. GDP consists of gemcitabine 1000 mg/m2 IV on Days 1 and 8, cisplatin 75 mg/m2 IV on Day 1, and dexamethasone 40 mg orally on Days 1 through 4. Epcoritamab will be administered subcutaneously (SC) on Days 1, 8, and 15. Patients will receive granulocyte colony stimulating factor (G-CSF) between Day 8 through Day 10 of each cycle of combination therapy.

Patients will then undergo radiology imaging for disease assessment. Patients may proceed to SCT(autologous or allogeneic) or CAR T-cell therapy or epcoritamab monotherapy upon completion of Cycle 3 per investigator discretion. The rationale for subjects not proceeding to autoSCT or CAR T-cell therapy will be captured in the eCRFs.

Patients who do not undergo SCT or CAR T-cell therapy may have the option to receive study treatment with epcoritamab monotherapy following completion of Cycle 3. Epcoritamab monotherapy will be offered to selected subjects who become ineligible to undergo SCT or CAR T-cell therapy (such as social situation, change in subject decision). The decision to offer epcoritamab monotherapy will be per investigator's discretion. However, subjects must have demonstrated a response to the combination therapy (partial remission or complete remission) per disease assessment scans prior to offering epcoritamab monotherapy. Epcoritamab monotherapy should begin 2 weeks following Cycle 3 Day 15. Monotherapy will consist of epcoritamab 48 mg administered subcutaneously on Days 1 and 15 of each 28 day cycle for Cycle 4 to Cycle 9 or until unacceptable toxicity, or disease progression per the Lugano Criteria.

Conditions

Large Cell Lymphoma, Diffuse; Relapsed Cancer; Refractory Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GDP + Epcoritamab + AutoSCT or CAR T-cell therapy

Cycles 1-3 (Cycle = 21 days) Epcoritamab will be administered by subcutaneous injection Days 1, 8, and 15. Epcoritamab Day 1: 0.16mg, Day 8: 0.8mg, Day 15: 48mg except Cycle 2-Epcoritamab will administered at 48mg on Days 1, 8 and 15

Gemcitabine will be administered by IV infusion on Days 1 and 8. Gemcitabine Days 1,8: 1,000mg/m^2

Cisplatin will be administered by IV infusion on Day 1. Cisplatin Day 1: 75mg/m^2

Dexamethasone will be given by mouth on Days 1-4. Dexamethasone Days 1-4: 40mg

After completion of Cycle 3 Autologous stem cell transplant (AutoSCT) OR CAR T-cell therapy

Group Type: EXPERIMENTAL

AutoSCT OR CAR T-cell Therapy

Intervention Type: PROCEDURE

Autologous stem cell transplant (AutoSCT) or CAR T-cell therapy will be performed after Cycle 3 of receiving epcoritamab and GDP

GDP

Intervention Type: DRUG

Gemcitabine Cisplatin Dexamethasone

Epcoritamab

Intervention Type: DRUG

Epcoritamab

GDP + Epcoritamab + Epcoritamab Maintenance

Cycles 1-3 (Cycle = 21 days) Epcoritamab will be administered by subcutaneous injection Days 1, 8, and 15 of each Cycle.

Epcoritamab Day 1: 0.16mg, Day 8: 0.8mg, Day 15: 48mg except Cycle 2-Epcoritabab will administered at 48mg on Days 1, 8 and 15

Gemcitabine will be administered by IV infusion on Days 1 and 8 of each Cycle. Gemcitabine Days 1,8: 1,000mg/m^2

Cisplatin will be administered by IV infusion on Day 1 of each Cycle. Cisplatin Day 1: 75mg/m^2

Dexamethasone will be given by mouth on Days 1-4 of Cycle 1 ONLY. Dexamethasone Days 1-4: 40mg

Cycles 4-9 (Cycle =28 Days) Epcoritamab will be administered by subcutaneous injection on Days 1, 8, and 15 of Cycles 4-9.

Group Type: EXPERIMENTAL

GDP

Intervention Type: DRUG

Gemcitabine Cisplatin Dexamethasone

Epcoritamab

Intervention Type: DRUG

Epcoritamab

Interventions

AutoSCT OR CAR T-cell Therapy

Autologous stem cell transplant (AutoSCT) or CAR T-cell therapy will be performed after Cycle 3 of receiving epcoritamab and GDP

Intervention Type: PROCEDURE

GDP

Gemcitabine Cisplatin Dexamethasone

Intervention Type: DRUG

Epcoritamab

Epcoritamab

Intervention Type: DRUG

Other Intervention Names

Autologous transplant; chimeric antigen receptor (CAR) T-cell

Eligibility Criteria

Inclusion Criteria

1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

2. Age ≥ 18 years at the time of consent.

3. ECOG Performance Status of 0-2 within 28 days prior to registration.

4. Histologically confirmed CD20+ relapsed large cell lymphoma according to the 5th edition of the WHO classification of the hematolymphoid tumors and the 2022 international consensus classification of mature lymphoid neoplasms. This includes de-novo and transformed from prior indolent B-cell NHL such as follicular lymphoma, or marginal zone lymphoma (33, 34). Subjects with high-grade B-cell lymphoma (HGBCL), NOS subtype, and high-grade B-cell lymphoma with c-MYC, Bcl2 and/or Bcl6 rearrangements (double or triple hit lymphoma) are eligible. Patients with primary mediastinal B-cell lymphoma, and T-cell histiocyte-rich B-cell lymphoma, primary cutaneous diffuse large B-cell lymphoma, leg type, Intravascular large B-cell lymphoma, Epstein-Barr virus-positive diffuse large B-cell lymphoma, NOS, Diffuse large B-cell lymphoma associated with chronic inflammation, and ALK-positive large B-cell lymphoma are eligible. Patients with Burkitt lymphoma or lymphoplasmacytic lymphoma are not eligible.

5. Positron emission tomography (PET) positive measurable disease with at least 1 node having the longest diameter (LDi) greater than (>) 1.5 centimeter (cm) or 1 extranodal lesion with LDi >1 cm (per the Lugano Criteria 2014).

6. Have received at least 1 prior line of systemic therapy for the treatment of large cell lymphoma. NOTE: Prior radiation therapy or systemic corticosteroids will not be considered a line of therapy.

7. Patients must be deemed eligible to proceed with stem cell transplantation (autologous or allogeneic) or CAR T-cell therapy per treating physician discretion. Patients being considered for allogeneic stem cell transplant may be eligible. Patients with prior stem cell transplantation or CAR T-cell therapy are eligible if they are deemed eligible to undergo another stem cell transplantation or CAR T-cell therapy.

8. Must have had relapsed or refractory disease following standard frontline chemotherapy. Refractory disease is defined as large cell lymphoma not achieving complete remission, progressing, or relapsing within 6 months after first-line chemotherapy based on PET/CT per the Lugano criteria. Relapsed disease is defined as disease that recurs beyond 6 months after completion of initial chemotherapy based on PET/CT per the Lugano criteria.

9. Archival tissue obtained within 2 years of signing consent is required if available and will be identified at screening and shipped prior to Cycle 2 Day 1. If archival tissue is not available, but the subject is undergoing a standard of care biopsy, fresh tissue from that standard of care biopsy may be used for eligibility. If a subject does not have archival tissue obtained within 2 years of signing consent or is not undergoing a standard of care biopsy, they are not eligible for the trial. Cytological or fine-needle aspiration samples are not acceptable. Tumor tissue from bone metastases that has been decalcified is not acceptable.

10. Demonstrate adequate organ function. All screening labs to be obtained within 21 days prior to registration. *Patients with bone marrow involvement will be eligible to participate in the study but must meet hematologic parameters.

11. Life expectancy of ≥ 6 months, as determined by the enrolling physician or protocol designee.

12. Females subjects of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study treatment. If a urine test is done and it is positice ir cannot be confirmed as negative, a serum pregnancy test will be required.

13. Female subjects of childbearing potential and male subjects must be willing to abstain from penile-vaginal intercourse or to use an effective method(s) of contraception.

14. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

Exclusion Criteria

1. Previous treatment with gemcitabine, cisplatin, and epcoritamab or other bispecific T-cell engager antibody (BsAB) such as glofitamab, mosunetuzumab, or odronextamab.

2. Known active central nervous system or meningeal involvement by large cell lymphoma at time of screening. Patients diagnosed with CNS disease who achieved and maintained CNS CR at the time of relapse are eligible. Lumbar puncture must be done in this case prior to study entry to demonstrate CNS CR status. Tests to investigate CNS involvement are required otherwise only if clinically indicated (i.e. disease suspected on basis of symptoms or other findings).

3. Contraindication to any drug contained in the combination therapy regimen (GDP).

4. Known hypersensitivity or allergic reaction to epcoritamab or its' excipients.

5. Use of any standard or experimental anti-large cell lymphoma therapy (including nonpalliative radiation, chemotherapy, immunotherapy, radio-immunotherapy, or any other anticancer therapy) < 14 days prior to C1D1. NOTE: Prednisone up to 50 mg or equivalent for 5 days is permitted; palliative radiation is permitted only if on non-target lesions).

6. Major surgery < 14 days of Cycle 1 Day 1.

7. Neuropathy Grade ≥ 2 (CTCAE v.5.0).

8. Patients with a history of other malignancies, except adequately treated non-melanoma skin cancer, non-invasive superficial bladder cancer, curatively treated in-situ cancer of the cervix, DCIS of the breast, localized low grade prostate cancer (up to Gleason score 6), or other solid tumours curatively treated with no evidence of disease for at least 3 years.

9. Active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) requiring systemic treatment within 7 days prior to the first dose of study treatment. Prophylactic antibacterial, antiviral, and antifungal agents are allowed.

10. Active HIV infection. NOTE: Testing for HIV antibody is required at the time of screening. Those with positive HIV antibody will require HIV viral load by PCR testing. Patients with detectable viral load will not be eligible for the study. Those with positive antibody but undetectable viral load and CD4 >200 will be eligible.

11. Testing for hepatitis B (HBV) and hepatitis C virus (HCV) is required at screening. Hepatitis B testing will consist of Hepatitis B surface Antigen (HBsAg), Hepatitis B Core Antibody (HBcAb) and Hepatitis Surface Antibody (HBsAb). Hepatitis C testing will consist of Hepatitis C Antibody (HCAb). Subjects with a history of chronic hepatitis B virus (HBV) infection must have an undetectable HBV viral load on suppressive therapy, if indicated. Subjects with evidence of prior HBV but who are PCR-negative are permitted in the trial but should receive prophylactic antiviral therapy. Subjects with a history of hepatitis C virus (HCV) infection must have been treated. For patients with HCV infection who are currently on treatment, the HCV viral load must be undetectable to be eligible for this trial. Subjects who received treatment for HCV that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable.

12. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).

13. Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety, or being compliant with the study procedures.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Genmab

INDUSTRY

Sponsor Role: collaborator

Dipenkumar Modi

OTHER

Sponsor Role: lead

Responsible Party

Dipenkumar Modi

Sponsor-Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Dipenkumar Modi, MD

Role: PRINCIPAL_INVESTIGATOR

Wayne State University

Locations

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, United States

Site Status: RECRUITING

Karmanos Cancer Center (Wayne State University)

Detroit, Michigan, United States

Site Status: RECRUITING

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status: RECRUITING

University of Virginia Health System

Charlottesville, Virginia, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Dipenkumar Modi, MD

Role: CONTACT

modid@karmanos.org

313-576-8739

Allison Lipps

Role: CONTACT

alipps@hoosiercancer.org

317-634-5842 ext. 40

Facility Contacts

Bobbie Frye

Role: primary

fryeba@iupui.edu

Mary Jo O'Loughlin

Role: primary

oloughli@karmanos.org

313-578-4405

Michael McCane

Role: primary

michael.mccane@utsouthwestern.edu

Sandy J Soler

Role: primary

dpt7xp@uvahealth.org

Other Identifiers

HCRN LYM22-565

Identifier Type: -

Identifier Source: org_study_id