Epcoritamab in Relapsed/Refractory Marginal Zone Lymphoma

Epcoritamab in Relapsed/Refractory Marginal Zone Lymphoma – Phase II Open‑Label Study

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What is this study about?

The study focuses on Marginal Zone Lymphoma, a rare, slow‑growing cancer of the immune system that can return or stop responding to standard treatments. The investigational medicine being evaluated is Tepkinly, a subcutaneous injection that contains the active substance Epcoritamab. This drug is designed to help the body’s own immune cells recognize and attack the lymphoma cells. Participants will receive a series of injections over several treatment cycles, with regular clinic visits to monitor health and any side effects.

The purpose of the trial is to assess how well the medication works and how safe it is for people with relapsed or refractory disease. The main goal is to determine the proportion of participants who achieve complete remission after the treatment course, while secondary goals include measuring the overall response rate, the length of time the disease stays controlled such as progression free survival, and the impact on patients’ quality of life. Throughout the study, participants will undergo routine examinations and questionnaires to track response, durability of benefit, and any adverse events.

1 enrollment and consent

after joining the study, you sign an informed consent form that explains the purpose, procedures, and possible risks of the trial.

your personal and medical information is recorded in the trial database.

2 baseline assessments

a series of examinations, laboratory tests, and imaging studies are performed to document the current status of marginal zone lymphoma.

the results are used to compare later measurements and to confirm eligibility for the treatment phase.

3 initial medication administration

the first dose of epcoritamab is given as a subcutaneous injection using the Tepkinly 4 mg/0.8 ml solution.

the dose for this initial injection is 3 mg.

the injection is performed by qualified medical staff in a clinical setting.

4 dose escalation and regular treatment cycles

subsequent doses are administered as subcutaneous injections using the Tepkinly 48 mg solution.

each of these injections contains a dose of 48 mg of epcoritamab.

the injections are given once per treatment cycle, and the treatment continues for up to 12 cycles unless early termination is required.

5 monitoring visits during treatment

before each injection, you attend a clinic visit where vital signs, physical examination, and laboratory tests are reviewed.

any side effects or adverse events are recorded and managed according to the trial protocol.

6 end‑of‑treatment evaluation

after completing 12 cycles, or at the time of early termination, a final assessment is performed four weeks later.

the assessment includes imaging and laboratory tests to determine the complete remission rate and other efficacy outcomes.

Who Can Join the Study?

You must have a confirmed diagnosis of marginal zone lymphoma (MZL) that tests positive for CD20 and is relapsed or refractory, with a tumor biopsy taken no more than 12 months before screening.
Men must agree not to father a child during the treatment period and for 4 months after the last dose, and they must use condoms; female partners must use a highly effective form of birth control.
You need measurable disease, meaning at least one tumor or affected area that can be sized on a scan (e.g., a lymph node larger than 1.5 cm, an organ lesion larger than 1.0 cm, spleen larger than 13 cm, or gastric involvement seen on endoscopy).
You must be willing and able to attend all scheduled visits, receive the study drug, undergo imaging and laboratory tests, and follow any study restrictions.
You must sign an informed consent form that shows you understand the disease, the experimental nature of the therapy, possible benefits, risks, side effects, and alternatives.
You must have symptoms that require systemic (whole‑body) treatment.
You must have previously received at least one anti‑CD20 monoclonal antibody (at least two treatment cycles) unless it was stopped early because the disease got worse or because of unacceptable side effects, and you must have failed to achieve at least a partial response or have disease progression after the most recent therapy. Treatment that only eradicates Helicobacter pylori or local radiation does not count.
Age must be 18 years or older.
Life expectancy must be longer than 3 months.
Baseline platelet count must be greater than 50 × 10⁹/L (unless low because the lymphoma has involved the bone marrow).
Absolute neutrophil count (ANC) must be greater than 1 × 10⁹/L (unless low because of lymphoma infiltration).
Circulating lymphocyte count must be less than 25 × 10⁹/L.
Hemoglobin must be at least 8.0 g/dL (or 5.6 mmol/L) without needing erythropoietin medication or a blood transfusion in the past two weeks.
Liver enzymes (ASAT/SGOT and ALAT/SGPT) must be less than three times the laboratory’s upper normal limit (or less than five times if lymphoma involves the liver).
Total bilirubin must be ≤ 1.5 times the upper limit of normal, or direct bilirubin ≤ 2 times the upper limit if total bilirubin is higher, unless the elevation is clearly due to the disease.
Serum creatinine must be ≤ 1.5 times the upper limit of normal, or kidney function (GFR) must be ≥ 50 mL/min if creatinine is higher.
Fibrinogen level must be at least 1 g/L.
Women of child‑bearing potential must have a negative pregnancy test (β‑hCG) at screening and enrollment, agree to use a highly effective method of birth control, and undergo monthly pregnancy testing during treatment and for 4 months after the last dose.
Highly effective birth control methods include hormonal contraception that prevents ovulation (pill, patch, ring, injection, implant), intrauterine devices (IUD/IUS), bilateral tubal occlusion, a vasectomised partner, or consistent sexual abstinence.

Who Cannot Join the Study?

ECOG performance status ≥ 3: This scale measures how well you can take care of yourself; a score of 3 means you need a lot of help with daily activities.
History of non‑infectious pneumonitis that required steroids, or current pneumonitis: Pneumonitis is inflammation of the lungs that is not caused by an infection.
Severe allergic reaction (anaphylaxis) to monoclonal antibodies or a severe (grade 3) allergy to the study drug or its ingredients: Monoclonal antibodies are laboratory‑made proteins used to treat disease.
History of another (non‑lymphoid) cancer except for certain early skin cancers, early‑stage prostate cancer, or other stage 1 cancers that have been cured and have stayed in complete remission for at least three years.
Active autoimmune disease that needed strong whole‑body medicines (systemic treatment) in the past two years: Autoimmune disease is when the immune system attacks the body’s own tissues; systemic treatment includes high‑dose steroids or other immune‑suppressing drugs.
Known past infection with tuberculosis (TB): TB is a bacterial infection that usually affects the lungs.
Ongoing alcohol or drug addiction, or psychiatric or substance‑abuse problems that would make it difficult to follow the study requirements.
History of Stevens‑Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN): These are severe, life‑threatening skin reactions.
Central nervous system lymphoma, leptomeningeal lymphoma, or transformation to a high‑grade lymphoma: Cancer involving the brain, spinal fluid, or an aggressive form of lymphoma.
Received chemotherapy or targeted small‑molecule therapy within 28 days before the first study dose, and any side effects must have improved to mild (grade 1) or less.
Previously treated with a bi‑specific anti‑CD20×CD3 antibody, a special type of experimental immune therapy.
Currently breastfeeding or pregnant.
Received any other experimental drug or participated in another clinical trial within 4 weeks (or longer based on the drug’s half‑life) before starting this study.
Had radiotherapy (radiation treatment) within 2 weeks before the first study dose.
Evidence of an active infection at the screening visit, such as a bacterial, fungal, or viral infection (examples: CMV, HIV, COVID‑19).
Ongoing drug‑induced liver injury or chronic liver diseases, including hepatitis B, alcoholic liver disease, non‑alcoholic steatohepatitis, primary biliary cholangitis, liver cirrhosis, or portal hypertension.
Known HIV infection, active hepatitis C or B infection, or any uncontrolled infection requiring IV antibiotics. People who only have vaccination markers for hepatitis B are allowed, but those with active virus (positive PCR test) are excluded.
Clinically significant cardiovascular disease, such as a heart attack within the past year, stroke within the past six months, or unstable/ uncontrolled heart problems (unstable angina, heart failure worse than NYHA class II, dangerous heart rhythm, or abnormal ECG) within the past three months.
Uncontrolled high blood pressure (arterial hypertension) despite medication.
Any other serious illness, medical condition, recent surgery, physical finding, ECG change, or lab abnormality that the doctor believes could make the study unsafe or affect the results.
Vaccination with a live vaccine (contains weakened live germs) within 30 days before starting treatment.
Recent blood‑clot events (thrombotic or embolic events) such as stroke, transient ischemic attack, deep‑vein thrombosis, or pulmonary embolism within the past three months.
Severe lung disease with interstitial involvement or very poor lung function, as judged by the doctor.
Active cancer spread to the brain or covering the brain membranes (active CNS metastases or carcinomatous meningitis). Previously treated brain metastases may be allowed if they have been stable on imaging for at least four weeks and have not required steroids for at least 14 days.

Where you can join this trial?

Verified and Recommended Sites

No sites found in this category

Verified Sites

Site Name	City	Country
University Hospital Jena KöR	Jena	Germany
Universitaetsmedizin Goettingen	Goettingen	Germany
Center For Pediatric And Adolescent Medicine Of The Johannes Gutenberg University Mainz	Mainz	Germany
Universitaetsklinikum Heidelberg AöR	Heidelberg	Germany
Rostock University Medical Center	Rostock	Germany

Other Sites

Site Name	City	Country
Institut fuer Klinische Transfusionsmedizin und Immungenetik Ulm gGmbH	Ulm	Germany
HELIOS Klinikum Emil von Behring GmbH	Berlin	Germany
Katholisches Klinikum Bochum gGmbH	Bochum	Germany
Institut Fuer Versorgungsforschung In Der Onkologie GbR	Koblenz	Germany
Udxvkuhetjnuztbonhtls Mohnbphi Asy	Munster	Germany
Kdcxxfwd dqb Ubddxnaeuyot Mkijgzur Acp	Munich	Germany
Ulpfskhros Mdejisk Cwmrdk Hfmijmwinxcyfxqdo	Hamburg	Germany
Mqzopvtnxvozaidoagxvdpsbcw Hpurrtxbdlwwwkff	Halle (Saale)	Germany

Trial status

Country	Status	Recruitment Start
Germany	Not yet recruiting	01.09.2026

Trial locations

Investigated drugs:

Epcoritamab

Tepkinly is a laboratory‑made medicine that contains the active substance epcoritamab. It works by helping the body’s immune system recognize and attack cancer cells in the lymph nodes. In this study, it is given as a small injection under the skin. The trial is testing whether Tepkinby can safely and effectively cause the lymphoma to disappear in people whose marginal‑zone lymphoma has come back or has not responded to other treatments.

Investigated diseases:

Marginal zone lymphoma – Marginal zone lymphoma is a cancer that starts in B‑cells located in the marginal zone of lymphoid tissue. It most often appears in the spleen, lymph nodes, or the gastrointestinal tract. The disease usually grows slowly, causing the involved organs to become enlarged. Over time the abnormal cells can spread to other parts of the lymphatic system or to the bone marrow. The condition progresses in stages, each reflecting a broader area of involvement.

Trial ID:

2025-524879-23-00

Protocol code:

EPOS-1

Trial Phase:

Therapeutic exploratory (Phase II)

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Epcoritamab in Relapsed/Refractory Marginal Zone Lymphoma – Phase II Open‑Label Study

What is this study about?

Who Can Join the Study?

Who Cannot Join the Study?