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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaet Muenster

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Sep 2025 → ongoing

Decision date (initial)

2025-09-15

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AbbVie Inc. · Swedish Orphan Biovitrum AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

best overall response rate (BORR), including complete and partial remissions, achieved up to 12-months of treatment

Secondary objectives 13

1. Progression-free survival (PFS)
2. Overall survival (OS)
3. Complete remission (CR) rate
4. Partial remission (PR) rate
5. Time to complete response
6. Time to best response
7. Duration of response
8. BORR after 18- and 24-months of treatment
9. Progression rate
10. Rate of relapse
11. Outcome according to biological characteristics of the lymphoma
12. Rate of treatment-related deaths
13. Safety and tolerability, and protocol adherence

Conditions and MedDRA coding

High-grade B-cell lymphoma (HGBL)

Regulatory references

Scientific advice from competent authorities

Paul-Ehrlich-Institut

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 21

1. Histologically confirmed relapsed/refractory DLBCL based on pathology report (WHO 2022 criteria): a. DLBCL (de novo or transformed), b. High-grade B-cell lymphoma with MYC and BCL2 rearrangements, c. High-grade B-cell lymphoma, not otherwise specified (NOS), d. Follicular lymphoma grade 3B
2. Total bilirubin ≤ 1.5 times the upper limit of normal (ULN), except for patients with Gilbert syndrome, cholestasis due to hepatic hilum adenopathies or liver involvement, or biliary obstruction due to lymphoma, who may have a total bilirubin ≤ 3 times the ULN
3. ALT and AST and GGT ≤ 2.5 times the ULN, or ≤ 5 times the ULN for patients with liver involvement by lymphoma
4. Glomerular filtration rate (GFR) ≥ 45 mL/min/1.73 m² according to the CKD-EPI formula. If not initially within target range, this evaluation may be repeated after at least 24 hours, either using the CKD-EPI formula or by 24-hour sampling. If the subsequent result is within the acceptable range, it may be used to fulfill the inclusion criteria
5. Prothrombin time/INR/aPTT ≤ 1.5 times the ULN, unless the patient is receiving anticoagulation (although the INR should not exceed 4.0)
6. Platelet count ≥ 75,000/mm³ without transfusion in the prior 7 days
7. Hemoglobin ≥ 8 g/dL
8. Absolute neutrophil count ≥ 1,000/mm3 (off growth factors at least 72 hours)
9. Left ventricular ejection fraction > 45%
10. Patients should not be taking any active medication known to decrease T-cell numbers or activity, or any other concurrent immunosuppressive medication, except for up to 10 mg of prednisone daily or an equivalent dose, unless it is necessary for disease control during the screening period, premedication and/or CRS/ICANS management within the study
11. The subject should not have been treated with any investigational drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to the first dose of the study drug. They should not be currently enrolled in another interventional clinical study or have been previously enrolled in this study, unless the agent being used has been approved under emergency authorization (e.g., anti-SARS-CoV-2 monoclonal antibodies)
12. Subject must be 18 years or older
13. The subject should not have received vaccination with live-attenuated vaccines within 28 days prior to screening, and they should not be expected to require any live-attenuated vaccination during their participation in the study, including at least 3 months following the last dose of study treatment. However, vaccination with coronavirus mRNA and adenovirus-based vaccines, which are not live-attenuated vaccines, is permitted
14. Subject must be eligible to receive and in need of treatment initiation based on symptoms and/or disease burden, as assessed by the investigator
15. Eastern Cooperative Oncology Group Performance (ECOG) status 0-2
16. Subjects must have r/r disease and have failed either first-line anti-CD20 monoclonal/anthracycline containing therapy administered at least one time and being CAR-T cell naive or have failed second-line CAR-T cell therapy
17. Subject must have one or more measurable disease sites defined as follows: a. A positron emission tomography/computed tomography (PET/CT) scan demonstrating PET- positive lesion(s) AND b. At least one measurable nodal lesion (long axis > 1.5 cm and short axis > 1.0 cm) or ≥ one measurable extra-nodal lesion (long axis > 1.0 cm) on CT scan or MRI
18. Ability to understand and willingness to sign written informed consent. Signed informed consent must be obtained before any study specific procedure
19. Women of childbearing potential and sexually active men must practice a highly effective method of birth control during and after the study, consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men with female partners who are of childbearing potential must agree to use a condom when sexually active or practice total abstinence from the time of giving informed consent until at least 7 months after the patient receives his last dose of study treatment. Men must agree not to donate sperm from the time of giving informed consent until at least 7 months after the patient receives his last dose of study treatment. For female subjects, they apply for 12 months after the last dose of the study drug
20. Women of childbearing potential participating in the study will be required to undergo a pregnancy test using either urine or serum beta-human chorionic gonadotropin (beta-hCG) at the screening visit. A negative result is necessary for inclusion in the study
21. Acute toxicity (except alopecia, fatigue) of any prior lymphoma therapy should be resolved to Grade ≤ 1 (with the exception of prior CRS or ICANS that should be fully resolved) at study screening

Exclusion criteria 29

1. Any prior lymphoma-directed therapy, except for first-line chemoimmunotherapy, or any treatment except first-line therapy and CAR-T cell therapy within second-line. Particularly, patients with prior loncastuximab tesirine and any CD3xCD20 bispecific antibody therapy cannot be considered
2. Known history of hypersensitivity and/or positive serum human anti-drug antibody (ADA) against any component of the study products or of the concomintant medication or an anti-CD19 antibody
3. History of Stevens-Johnson syndrome or toxic epidermal necrolysis
4. Clinically significant third space fluid accumulation, such as ascites requiring drainage or pleural effusion that either requires drainage or is associated with shortness of breath
5. Pregnancy or breastfeeding
6. Use of any other experimental medication within 30 days or 5 half-lives prior to the start of the study drug (Cycle 1 Day 1)
7. Close affiliation with the investigational site, such as being a close relative of the investigator or dependent person (e.g., employee or student of the investigational site)
8. Congestive heart failure > New York Heart Association (NYHA) class 2
9. Unstable angina (angina symptoms at rest) or new-onset angina (begun within the last 3 months)
10. Uncontrolled atrial or ventricular cardiac arrhythmia
11. Left ventricular ejection fraction ≤ 45%
12. Known central nervous system (CNS) involvement
13. Electrocardiographic evidence of acute ischemia, coronary angioplasty, or myocardial infarction within 6 months prior to screening
14. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within 3 months before the start of study medication
15. Congenital long QT syndrome or a QTcF interval of > 480 ms at screening (unless secondary to pacemaker or bundle branch block)
16. Severe chronic pulmonary disease
17. Known clinically significant liver disease, including hepatitis, current alcohol abuse, or cirrhosis
18. Autoimmune disease requiring immunosuppressive therapy, except for up to 10 mg prednisone daily (or equivalent)
19. Seizure disorder requiring therapy within the past 12 months. Subjects with a history of seizure disorder beyond must have a complete CNS workup
20. Major surgery within 4 weeks of the first dose of study drugs, except for lymphoma reasons
21. Any other co-existing medical or psychological condition that will preclude participation in the study or compromise the ability to give informed consent
22. 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
23. 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
24. CMV-PCR positive at baseline
25. 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)
26. Concurrent treatment with another investigational agent or radiation therapy
27. 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
28. Participation in another clinical trial
29. Patients with late relapse (>12 months) after first-line immunochemotherapy considered HDCT/ASCT eligible as assessed by the local investigator.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is the 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, as assessed by local investigator review

Secondary endpoints 17

1. 2-year progression-free survival (PFS) with a 95% confidence interval. PFS is defined as time from the first dose of study drug until one of the following events occurs, whichever is first: Disease progression, Relapse, Death due to any cause. Patients who have not experienced an event at the time of analysis will be censored at the most recent date of disease assessment
2. 2-year overall survival (OS) defined as the time from the first dose of study drug to death of any cause. Patients who have not experienced an event at the time of analysis will be censored at the last date known to be alive.
3. Complete response (CR) rate measured as the number of complete remissions as best response (achieved up to 12 months) divided by the number of patients treated with at least one dose of study drug
4. Partial response (PR) rate measured as the number of partial remissions as best response (achieved up to 12 months) divided by the number of patients treated with at least one dose of study drug
5. Time to complete response measured as the time from the start of therapy to documentation of complete remission
6. Time to best response (achieved up to 12 months) measured as the time from the start of therapy to documentation of the best tumor response according to type of response
7. Duration of response measured as the time from documentation of tumor response (complete or partial remission) to relapse or progressive disease
8. BORR defined as the best overall response of complete or partial remission after 18- and 24-months of treatment
9. Progression rate measured as the number of progressions (observed up to 12 months) divided by the number of patients treated with at least one dose of study drug
10. Relapse rate measured as the number of relapses divided by the number of patients included with complete or partial remission
11. Outcomes according to biological characteristics of the lymphoma
12. Adverse Events
13. Serious Adverse Events
14. Rate of treatment-related deaths defined as the number of treatment-related deaths during therapy or up to 2 months after the end of therapy divided by the number of patients included
15. Number of treatment cycles received
16. Duration of treatment cycles
17. Cumulative doses of loncastuximab tesirine and epcoritamab

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaet Muenster

Sponsor organisation

Universitaet Muenster

Address

Schlossplatz 2, Schlossbezirk Schlossbezirk

City

Muenster

Postcode

48149

Country

Germany

Scientific contact point

Organisation

Universitaet Muenster

Contact name

Georg Lenz

Public contact point

Organisation

Universitaet Muenster

Contact name

Georg Lenz

Locations

1 EU/EEA country · 35 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 4 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications