Epcoritamab Plus Standard of Care Platinum-Based Chemotherapy and Autologous Hematopoietic Cell Transplant for the Treatment of Relapsed or Refractory Large B-cell Lymphoma

NCT06905509 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: UCDCC316NCI-2025-01557P30CA093373
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial tests how well epcoritamab in combination with standard of care (SOC) platinum-based chemotherapy (rituximab, ifosfamide, carboplatin, etoposide \[RICE\], rituximab, cytarabine, dexamethasone, oxaliplatin or carboplatin RDHAP/X\] or gemcitabine and oxaliplatin \[Gem/Ox\]) and autologous hematopoietic cell transplant (HCT) works in treating patients with large B-cell lymphoma (LBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Epcoritamab, a type of bispecific T-cell engager, binds to a protein called CD3, which is found on T cells (a type of white blood cell). It also binds to a protein called CD20, which is found on B cells (another type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells and some types of cancer cells. This may help the immune system kill cancer cells. Chemotherapy drugs, such as ifosfamide, etoposide phosphate, cytarabine, and gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. An autologous HCT is a procedure in which blood-forming stem cells (cells from which all blood cells develop) are removed, stored, and later given back to the same person. Giving epcoritamab in combination with SOC platinum-based chemotherapy, such as RICE, RDHAP/X and Gem/Ox, and autologous HCT may kill more cancer cells in patients with relapsed or refractory LBCL.

Conditions

Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Recurrent High Grade B-Cell Lymphoma With MYC and BCL2 Rearrangements; Recurrent High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements; Recurrent High Grade B-Cell Lymphoma, Not Otherwise Specified; Recurrent Nodal Marginal Zone Lymphoma; Recurrent Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma, Not Otherwise Specified; Refractory High Grade B-Cell Lymphoma With MYC and BCL2 Rearrangements; Refractory High Grade B-Cell Lymphoma With MYC and BCL6 Rearrangements; Refractory High Grade B-Cell Lymphoma, Not Otherwise Specified; Refractory Nodal Marginal Zone Lymphoma; Refractory Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Complete response rate (CRR)

  Will be assessed by Lugano 2014. Will be calculated as the number of participants achieving complete response divided by the number of evaluable patients. CRR will be presented alongside the corresponding exact binomial 95% confidence interval.

  From first dose up to 2 years post-autologous hematopoietic cell transplantation (autoHCT) therapy

Secondary Outcomes (6)

• Incidence of treatment-related adverse events (AEs)

  From first dose through 30 days post last epcoritamab dose

• Progression-free survival

  From the date of enrollment until the first occurrence of disease progression, or death from any cause, whichever occurs first, assessed up to 2 years post-autoHCT therapy

• Objective response

  From first dose up to 2 years post-autoHCT therapy

• Overall survival

  From first dose to death due to any causes, assessed up to 2 years post-autoHCT therapy

• Duration of minimal residual disease (MRD) negativity

  Pre-autoHCT and 90 days post-autoHCT

Study Arms (1)

Treatment (epcoritamab, SOC chemotherapy, autoHCT)

EXPERIMENTAL

See Detailed Description

Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carboplatin; Drug: Cytarabine; Drug: Dexamethasone; Biological: Epcoritamab; Drug: Etoposide Phosphate; Drug: Gemcitabine; Drug: Ifosfamide; Procedure: Multigated Acquisition Scan; Drug: Oxaliplatin; Biological: Rituximab

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autoHCT

Also known as: AHSCT, Autologous, Autologous Hematopoietic Cell Transplantation, Autologous Stem Cell Transplant, Autologous Stem Cell Transplantation, Stem Cell Transplantation, Autologous

Treatment (epcoritamab, SOC chemotherapy, autoHCT)

Carboplatin DRUG

Given carboplatin

Also known as: Blastocarb, Carboplat, Carboplatin Hexal, Carboplatino, Carboplatinum, Carbosin, Carbosol, Carbotec, CBDCA, Displata, Ercar, JM-8, JM8, Nealorin, Novoplatinum, Paraplatin, Paraplatin AQ, Paraplatine, Platinwas, Ribocarbo

Treatment (epcoritamab, SOC chemotherapy, autoHCT)

Cytarabine DRUG

Given cytarabine

Also known as: .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-Beta-D-arabinofuranosylcytosine, 1.beta.-D-Arabinofuranosylcytosine, 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-, 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-, Alexan, Ara-C, ARA-cell, Arabine, Arabinofuranosylcytosine, Arabinosylcytosine, Aracytidine, Aracytin, Aracytine, Beta-Cytosine Arabinoside, CHX-3311, Cytarabinum, Cytarbel, Cytosar, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453

Treatment (epcoritamab, SOC chemotherapy, autoHCT)

Dexamethasone DRUG

Given dexamethasone

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, LenaDex, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Treatment (epcoritamab, SOC chemotherapy, autoHCT)

Epcoritamab BIOLOGICAL

Given SC

Also known as: Anti-CD20/CD3 Bispecific Antibody GEN3013, DuoBody-CD3xCD20, Epcoritamab-bysp, Epkinly, GEN 3013, GEN-3013, GEN3013, Tepkinly

Treatment (epcoritamab, SOC chemotherapy, autoHCT)

Etoposide Phosphate DRUG

Given etoposide phosphate

Also known as: Etopophos

Treatment (epcoritamab, SOC chemotherapy, autoHCT)

Gemcitabine DRUG

Given gemcitabine

Also known as: dFdC, dFdCyd, Difluorodeoxycytidine

Treatment (epcoritamab, SOC chemotherapy, autoHCT)

Ifosfamide DRUG

Given ifosfamide

Also known as: Asta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942

Treatment (epcoritamab, SOC chemotherapy, autoHCT)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (epcoritamab, SOC chemotherapy, autoHCT)

Oxaliplatin DRUG

Given oxaliplatin

Also known as: 1-OHP, Ai Heng, Aiheng, Dacotin, Dacplat, Diaminocyclohexane Oxalatoplatinum, Eloxatin, Eloxatine, Elplat, JM 83, JM-83, JM83, Oxalatoplatin, Oxalatoplatinum, RP 54780, RP-54780, RP54780, SR 96669, SR-96669, SR96669

Treatment (epcoritamab, SOC chemotherapy, autoHCT)

Rituximab BIOLOGICAL

Given rituximab

Also known as: ABP 798, ABP-798, ABP798, BI 695500, BI-695500, BI695500, Blitzima, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT P10, CT-P10, CTP10, GP 2013, GP-2013, GP2013, IDEC 102, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, IDEC102, Ikgdar, Mabtas, MabThera, Monoclonal Antibody IDEC-C2B8, PF 05280586, PF-05280586, PF05280586, Riabni, Ritemvia, Rituxan, Rituximab ABBS, Rituximab ARRX, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar GB241, Rituximab Biosimilar GP2013, Rituximab Biosimilar IBI301, Rituximab Biosimilar JHL1101, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, Rituximab Biosimilar SIBP-02, rituximab biosimilar TQB2303, Rituximab PVVR, Rituximab-abbs, Rituximab-arrx, Rituximab-blit, Rituximab-pvvr, Rituximab-rite, Rituximab-rixa, Rituximab-rixi, Rixathon, Riximyo, RTXM 83, RTXM-83, RTXM83, Ruxience, Truxima

Treatment (epcoritamab, SOC chemotherapy, autoHCT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must have histologically or cytologically confirmed R/R LBCL
• Can include diffuse large B-cell lymphoma (DLBCL) (not otherwise specified \[NOS\] or with concurrent MYC and BCL2 rearrangements), high-grade B-cell lymphoma (HGBCL) (NOS or with MYC and BCL2 or BCL6 rearrangements) and transformed follicular lymphoma (FL) and nodal marginal zone lymphoma (MZL)
• Histological confirmed CD20+ relapsed/ refractory large cell lymphoma
• 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
• Have received 1 or more prior lines 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
• Candidate for platinum-containing chemotherapy (RICE, RDHAP/X, or R-Gem/Ox) pre-autologous hematopoietic cell transplantation (autoHCT) followed by autoHCT as per institutional guidelines
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%)
• Measurable disease via diagnostic quality CT or PET/CT 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)
• Aged ≥ 18 at the time of consent
• Creatinine clearance (CrCl) ≥ 45 mL/min (Cockcroft-Gault)
• Serum alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN)
• Serum aspartate aminotransferase (AST) ≤ 3 x ULN
• Bilirubin ≤ 1.5 x ULN unless due to Gilbert's syndrome or controlled autoimmune hemolytic anemia (not requiring immunosuppressive other than ≤ 20 mg of prednisolone daily)
• Note: Patients with Gilbert's syndrome may be included if total bilirubin is ≤ 3 x ULN and direct bilirubin is ≤ 1.5 x ULN
• Hemoglobin ≥ 8.0 g/dL

You may not qualify if:

• Any adverse event (AE) related to the previous large cell lymphoma therapy which has not recovered to grade ≤ 1 (Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\] 5.0) or baseline by cycle 1 day 1 (C1D1), except alopecia and non-clinically significant laboratory abnormalities
• Uncontrolled intercurrent illness (including infection)
• Known active central nervous system or meningeal (including leptomeningeal) involvement. Patients diagnosed with central nervous system (CNS) disease who achieved and maintained CNS complete response (CR) at the time of relapse are eligible. Lumbar puncture must be done in this case prior to study entry (within 90 days of enrollment) 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)
• Receiving any other investigational treatments
• Previous treatment with any bispecific T-cell engager with or without chemotherapy
• Treatment with an investigational drug within 4 weeks or 5 half-lives, whichever is longer, prior to the first dose of epcoritamab
• Concurrent use of other anti-cancer agents or treatments except for certain therapeutics (e.g., prostate, breast hormonal-based therapy) per the treating physician's discretion
• Standard agents within 2 weeks or 5 half-lives, whichever is shorter, prior to the first dose of epcoritamab (excluding anti-CD20 monoclonal antibodies \[mAbs\], which can be administered until first full dose of epcoritamab); or
• CAR-T cell therapy within 30 days prior to the first dose of epcoritamab
• Palliative radiation is permitted only if on non-target lesions
• Motor and sensory neuropathy grade ≥ 2 (CTCAE v.5.0)
• 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, ductal carcinoma in situ (DCIS) of the breast, localized low grade prostate cancer (up to Gleason score 6), or other solid tumors curatively treated with no evidence of disease for at least 3 years
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at trial enrollment or significant infections within 2 weeks prior to the first dose of epcoritamab
• Confirmed history or current autoimmune disease or other diseases requiring permanent immunosuppressive therapy. Low-dose (10 mg/day) prednisolone (or equivalent) for rheumatoid arthritis or similar conditions is allowed
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study)

Sponsors & Collaborators

• Joseph Tuscano: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell, Marginal Zone

Interventions

Stem Cell Transplantation; Carboplatin; Cytarabine; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; etoposide phosphate; Gemcitabine; Ifosfamide; Oxaliplatin; Rituximab; CT-P10

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Coordination Complexes; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Deoxycytidine; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Oxazines; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Joseph M Tuscano

  University of California, Davis

  STUDY CHAIR

Central Study Contacts

Selina Laqui

CONTACT

916-734-0565; sblaqui@ucdavis.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 25, 2025
• First Posted: April 1, 2025
• Study Start: July 31, 2025
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): August 1, 2030
• Last Updated: September 29, 2025

Record last verified: 2025-09

Locations

US (1)