Combining Loncastuximab Tesirine and Epcoritamab in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

NCT07197307 | Recruiting Phase 2 DMC

• 2 other identifiers: WWU23_00062023-509861-19-01
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 34

Brief Summary

This is a phase II study designed to evaluate the toxicity and efficacy of the combination of loncastuximab tesirine and epcoritamab in patients with relapsed/refractory aggressive B-cell lymphoma. Chimeric antigen receptor (CAR)-T cell naive patients who have failed first-line therapy and patients who have received CAR-T cells as second-line therapy and experienced CAR-T failure will be eligible for inclusion.

Conditions

Aggressive Diffuse Large B-cell Lymphoma; High-grade B-cell Lymphoma (HGBL); Follicular Lymphoma (FL) Grade 3B

Keywords

Loncastuximab Tesirine; Epcoritamab; Diffuse Large B-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Best overall response rate (BORR)

  BORR defined as the proportion of patients with r/r DLBCL, HGBL and FL grade 3B who achieve a complete or partial remission as best response up to 12-months of study treatment according to the 2014 Lugano criteria.

  12 months after the start of study therapy

Secondary Outcomes (14)

• Progression-free survival (PFS)

  2 years after the start of study therapy

• Overall survival (OS)

  2 years after the start of study therapy

• Complete response (CR) rate

  12 months after the start of study therapy

• Partial response (PR) rate

  12 months after the start of study therapy

• Time to complete response

  from the start of therapy to documentation of complete remission

Study Arms (1)

Loncastuximab Tesirine and Epcoritamab

EXPERIMENTAL

Combination of loncastuximab tesirine and epcoritamab in patients with relapsed/refractory aggressive B-cell lymphoma (DLBCL, HGBL or FL grade 3B)

Drug: Loncastuximab Tesirine and Epcoritamab

Interventions

Loncastuximab Tesirine and Epcoritamab DRUG

Loncastuximab tesirine: Loncastuximab tesirine 150 µg/kg iv for 2 cycles followed by 75 µg/kg iv on day 1 of each 21-day cycle in responding patients for 4 cycles subsequently (max. 6 cycles). Epcoritamab: Step-up dosing for epcoritamab sc will be performed, consisting of a 0.16 mg sc priming dose on day 1 of cycle 1 (day 8 of cycle 1 for loncastuximab tesirine), followed by a 0.8 mg sc dose on day 8, and full dosing with 48 mg sc on day 15. Starting from day 15, epcoritamab will be administered weekly during cycle 2-3, then once every 2 weeks during cycle 4-9, and once every 4 weeks from cycle 10 until cycle 13 (max. 13 cycles).

Loncastuximab Tesirine and Epcoritamab

Eligibility Criteria

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

You may qualify if:

• Disease:
• Subjects with histologically confirmed relapsed/refractory DLBCL based on pathology report (WHO 2022 criteria)
• DLBCL (de novo or transformed)
• High-grade B-cell lymphoma with MYC and BCL2 rearrangements
• High-grade B-cell lymphoma, not otherwise specified (NOS)
• Follicular lymphoma grade 3B
• Diagnostic biopsy performed at the time of relapse/progressive disease no longer than 3 months before study entry must be available, with sufficient material for central review and complimentary scientific analyses. CD20 expression (or a high likelihood of CD20 expression) based on immunohistochemistry should be documented prior enrollment into the study.
• Refractory disease is defined as no remission to the last therapy. Subjects intolerant to previous therapy are excluded. Two groups of patients are eligible:
• Progressive disease (PD) or stable disease (SD) as best response to previous therapy.
• Complete (CR) or partial response (PR) as the best response after previous therapy, with biopsy-proven relapse occurring \< 6 months after end of treatment.
• Relapsed disease is defined as subjects achieving complete or partial remission to previous therapy, followed by biopsy-proven relapse ≥6 months after treatment completion.
• Subjects with refractory and early relapsed (≤12 months) disease after first line anti-CD20-/anthracycline-containing therapy are eligible. Subjects with late relapsed (\>12 months) disease after first line anti-CD20-/anthracycline-containing therapy can be enrolled in the study only if deemed ineligible to high dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT)) or if refuse to undergo HDCT/ASCT. Subjects relapsed/refractory to second line CAR-T cell therapy are eligible.
• Subject must be 18 years or older.
• Subject must be eligible to receive and in need of treatment initiation based on symptoms and/or disease burden, as assessed by the investigator.
• Eastern Cooperative Oncology Group Performance (ECOG) status 0-2.

You may not qualify if:

• Patients who meet any of the following criteria at the time of screening will be excluded:
• Any prior lymphoma-directed treatment, except for first-line anti-CD20-/anthracycline-containing chemoimmunotherapy or second line CAR-T cell therapy. Particularly, patients previously treated with loncastuximab tesirine and any CD3xCD20 bispecific antibody therapy are not eligible.
• Patients with late relapse (\>12 months) after first-line immunochemotherapy considered HDCT/ASCT eligible as assessed by the local investigator.
• Known central nervous system (CNS) involvement.
• Diagnosed or treated for any malignancy other than r/r DLBCL, HGBL or FL grade 3B within the last 3 years, except for adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, non-invasive basal cell or squamous cell skin carcinoma, adequately treated carcinoma in situ without evidence of disease, localized prostate cancer, post-radical prostatectomy with non-rising prostate-specific antigen levels \< 0.1 ng/mL, cervical carcinoma of stage 1B or less, non-invasive, superficial bladder cancer or any curable cancer with a CR of \> 2 years duration.
• Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or active hepatitis B virus (HBV) infection or any known active systemic bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds). Patients with serologic markers of HBV immunization due to vaccination (HBsAg negative, Anti-HBc negative, and Anti-HBs positive) will be eligible. Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
• Cytomegalovirus (CMV)-PCR positive at baseline.
• Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or interfere with the feasibility to administer study drugs including active hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), history of cutaneous collagenous vasculopathy and capillary leak syndrome.
• Concurrent treatment with another investigational agent or radiation therapy.
• Any psychological, cognitive, familial, or social condition that, in the investigator's opinion, compromises the patient's ability to understand the patient information, give informed consent, or comply with the study protocol.
• Participation in another clinical trial.
• Known history of hypersensitivity and/or positive serum human anti-drug antibody (ADA) against any component of the study products or of the concomitant medication or an anti-CD19 antibody.
• History of Stevens-Johnson syndrome or toxic epidermal necrolysis.
• Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath; history of pericardial effusion).
• Pregnancy or breastfeeding.

Sponsors & Collaborators

• Universität Münster: lead
• AbbVie: collaborator
• Sobi, Inc.: collaborator

Study Sites (34)

Universitaetsklinikum Aachen

Aachen, 52074, Germany

RECRUITING

Universitaetsklinikum Augsburg

Augsburg, 86156, Germany

RECRUITING

Vivantes Netzwerk fuer Gesundheit

Berlin, 10967, Germany

RECRUITING

Charite Universitaetsmedizin Berlin

Berlin, 12203, Germany

RECRUITING

HELIOS Klinikum Berlin-Buch

Berlin, 13125, Germany

RECRUITING

Evangelisches Klinikum Bethel

Bielefeld, 33611, Germany

RECRUITING

Klinikum Chemnitz

Chemnitz, 09116, Germany

RECRUITING

Universitaetsklinikum Duesseldorf

Düsseldorf, 40225, Germany

RECRUITING

Universitaetsklinikum Erlangen

Erlangen, 91054, Germany

RECRUITING

Universitaetsklinikum Essen

Essen, 45147, Germany

NOT YET RECRUITING

Universitaetsklinikum Frankfurt

Frankfurt, 60590, Germany

RECRUITING

Medical Center - University Of Freiburg

Freiburg im Breisgau, 79106, Germany

RECRUITING

Universitaetsmedizin Greifswald

Greifswald, 17489, Germany

RECRUITING

Universitaetsklinikum Halle (Saale)

Halle, 06120, Germany

RECRUITING

University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

NOT YET RECRUITING

St. Barbara-Klinik Hamm

Hamm, 59073, Germany

RECRUITING

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Universitaet Des Saarlandes

Homburg, 66421, Germany

RECRUITING

Universitaetsklinikum Jena

Jena, 07747, Germany

RECRUITING

Staedtisches Klinikum Karlsruhe

Karlsruhe, 76133, Germany

RECRUITING

Universitaetsklinikum Schleswig-Holstein

Kiel, 24105, Germany

RECRUITING

Universitaetsklinikum Schleswig-Holstein

Lübeck, 23538, Germany

RECRUITING

Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz

Mainz, 55131, Germany

RECRUITING

Philipps-Universitaet Marburg

Marburg, 35043, Germany

RECRUITING

Muehlenkreiskliniken

Minden, 32429, Germany

RECRUITING

Kliniken Ostalb gemeinnuetzige kommunale Anstalt des oeffentlichen Rechts

Mutlangen, 73557, Germany

RECRUITING

Klinikum der Universitaet Muenchen

München, 81377, Germany

NOT YET RECRUITING

Universitätsklinikum Münster, Medizinische Klinik A

Münster, 48149, Germany

RECRUITING

Ortenau Klinikum

Offenburg, 77654, Germany

RECRUITING

Klinikum Oldenburg

Oldenburg, 26133, Germany

RECRUITING

Medizinisches Versorgungszentrum des Bruederkrankenhauses St. Josef Paderborn

Paderborn, 33098, Germany

RECRUITING

Universitaetsklinikum Regensburg

Regensburg, 93053, Germany

RECRUITING

Diakonie-Klinikum Stuttgart Diakonissenkrankenhaus und Paulinenhilfe

Stuttgart, 70176, Germany

NOT YET RECRUITING

Universitaetsklinikum Ulm

Ulm, 89081, Germany

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular; Lymphoma, Large B-Cell, Diffuse

Interventions

loncastuximab tesirine

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Georg Lenz, Prof.

CONTACT

+492518347587; lenzsekr@ukmuenster.de

Study Design

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

Study Record Dates

• First Submitted: September 3, 2025
• First Posted: September 29, 2025
• Study Start: October 31, 2025
• Primary Completion (Estimated): April 30, 2030
• Study Completion (Estimated): April 30, 2030
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (34)