Epcoritamab in Relapsed/Refractory Marginalzone Lymphoma - A MULTICENTER OPEN LABEL SINGLE-ARM PHASE II STUDY (EPOS-1)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Universitaetsklinikum Ulm AöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Decision date (initial)

2026-06-19

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

AbbVie

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

The objective of the trial is to test the efficacy and safety of the treatment of Epcoritamab SC in participants with relapsed/refractory MZL. For efficacy, the rate of complete remissions after therapy will be primarily analysed. For toxicity, treatment associated adverse events, quality of life, and cumulative incidence of secondary malignancies will be documented.

Conditions and MedDRA coding

Marginal Zone Lymphoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 20

1. Participants must have a proven pathological diagnosis of MZL, confirmed by a reference pathology center: -Confirmed CD20-positive relapsed/refractory extranoda Lymphoma or -Confirmed CD20-positive relapsed/refractory splenic MZL or -Confirmed CD20-positive relapsed/refractory nodal MZL A tumor biopsy not older than 12 months is required at screening for confirming diagnosis in all participants.
2. Circulating lymphocytes < 25 G/l
3. ASAT (SGOT): < 3.0 times the upper limit of institutional laboratory normal value or < 5 times the upper limit of institutional laboratory normal value in subjects with lymphoma in the liver
4. ALAT (SGPT): < 3.0 times the upper limit of institutional laboratory normal value or < 5 times the upper limit of institutional laboratory normal value in subjects with lymphoma in the liver
5. Serum total bilirubin: ≤ 1.5 × ULN OR Direct bilirubin ≤ 2 x ULN for subjects with total bilirubin levels > 1.5 ULN (unless clearly related to the disease)
6. Serum creatinine ≤1.5 × ULN OR ≥ 50 mL/min GFR or CrCl for subjects with creatinine levels > 1.5 × institutional ULN
7. Fibrinogen must be ≥ 1 g/L
8. For women of child-bearing potential (WOCBP) only: Pregnancy β-HCG negative. Serum or urine β-HCG must be negative during screening and at study enrolment visit.
9. WOCBP (criteria listed in Appendix C) must agree to use a highly effective method of birth control and to a monthly pregnancy test for the duration of the therapy up to 4 months after the last dose of Epcoritamab. A highly effective method of birth control is defined as those which results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS), bilateral tubal occlusion, vasectomised partner or sexual abstinence. Contraception and pregnancy testing are required according the CTFG recommendations (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf)
10. Men must agree not to father a child for the duration of therapy and 4 months after the last dose of Epcoritamab as well as to advice a female partner to use a highly effective method of birth control. According to CTFG recommendations, men must use condoms.
11. Measurable and/or evaluable disease: at least one bi-dimensionally measurable lesion (a measurable node must have a longest transverse diameter of a lesion (LDi) > 1.5 cm. A measurable extranodal lesion should have an LDi > 1.0 cm by CT/ PET-CT scan or MRI. Please refer to Appendix D, Splenomegaly > 13 cm is considered to be measurable disease (splenic MZL), for gastric MZL without any other lymphoma manifestations gastric infiltration as determined by gastroendoscopy is considered to be measurable disease (see Appendix E)
12. Willingness and ability to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions
13. Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, possible side effects, potential risks and discomforts, and other pertinent aspects of study participation.
14. symptomatic participants in need of systemic treatment
15. Previously treated with at least one anti-CD20 monoclonal antibody at least 2 cycles, unless discontinued earlier due to documented disease progression or unacceptable toxicity. Must have a documented failure to achieve at least PR during the most recent systemic therapy or documented progressive disease after the most recent systemic therapy. Systemic therapy does not include Helicobacter pylori eradication or local involved field radiotherapy.
16. Age ≥ 18 years
17. Life expectancy >3 months.
18. Baseline platelet count >50x109/L (if not due to BM infiltration by the lymphoma)
19. ANC > 1x109//G (unless lower counts are due to lymphoma infiltration).
20. Hemoglobin ≥ 8.0 g/dL or ≥ 5.6 mmol/L (Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks)

Exclusion criteria 24

1. ECOG performance status ≥ 3
2. Breastfeeding or Pregnancy
3. Clinically significant cardiovascular disease, including the following: • Myocardial infarction within 1 year or stroke within 6 months prior to randomization OR • The following conditions within 3 months prior to randomization: unstable or uncontrolled disease/condition related to or affecting cardiac function (e.g., unstable angina (angina symptoms at rest; new onset angina starting within the last 3 months), congestive heart failure > New York Heart Association (NYHA) class II), uncontrolled cardiac arrhythmia, or other clinically significant electrocardiogram (ECG) abnormalities in the opinion of the investigator
4. Uncontrolled arterial hypertension despite optimal medical management
5. Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject or impair the assessment of study results
6. Vaccination with a live vaccine within 30 days prior to start of therapy
7. 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.
8. History of severe concurrent interstitial lung and/or severely impaired lung function (as judged by the investigator)
9. Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e. without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study treatment
10. Has a history of non-infectious pneumonitis that required steroids, or current pneumonitis
11. History of anaphylaxis in association with previous administration of monoclonal antibodies or severe hypersensitivity (≥ Grade 3) to the investigational medicinal product and/or any of its excipients
12. History of a non-lymphoid malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for ≥1 year prior to study enrolment visit, other Stage 1 cancer treated with a curative intent and currently in complete remission, for ≥3 years
13. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Systemic corticosteroid treatment <20 mg/day prednisone or equivalent and inhaled corticosteroids are permitted. Last dose of corticosteroid ≥20 mg/day prednisone or equivalent will not be permitted during the last 7 days before inclusion.
14. Has a known history of TB (Bacillus Tuberculosis)
15. Ongoing alcohol or drug addiction or known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
16. History of Diagnosis of Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necrolysis (TEN)
17. Central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of transformation to a high-grade or diffuse large B-cell lymphoma
18. Has had prior chemotherapy (systemic anti-cancer therapy) or targeted small molecule therapy within 28 days prior to study Day 1. Non-hematologic toxicity must be recovered to ≤ grade 1 before inclusion.
19. Has received prior therapy with a bi-specific anti-CD20xCD3 antibody
20. Treatment with any other investigational agent or participating in another clinical trial with an investigational product within 4 weeks prior to entering this study or within 5 x the half-life (t1/2) of the investigational product, whichever is longer
21. Has received prior radiotherapy within 2 weeks of start of study treatment.
22. Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of study enrolment visit, such as CMV, HIV, SARS-COV-2.
23. Ongoing drug-induced liver injury, chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cholangitis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension
24. Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or active hepatitis B virus (HBV) infection or any uncontrolled active systemic infection requiring IV antibiotics. Participants 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 enrolment. Those who are PCR positive will be excluded.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. CR rate (CRR) determined 4 weeks after the end of treatment (after 12 cycles of treatment or in the case of early termination at the time point of the early termination visit)

Secondary endpoints 11

1. Overall response rate (ORR) after12 cycles of treatment
2. Best response (BR): CR and ORR
3. Time to best response: CR, ORR
4. Time to first response: CR, ORR
5. Progression free survival (PFS)
6. Time to treatment failure (TTF)
7. Duration of Response (DR)
8. Cause specific survival (CSS)
9. Overall survival (OS)
10. Quality of life
11. Safety

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Universitaetsklinikum Ulm AöR

Sponsor organisation

Universitaetsklinikum Ulm AöR

Address

Albert-Einstein-Allee 29, Eselsberg Eselsberg

City

Ulm

Postcode

89081

Country

Germany

Scientific contact point

Organisation

Universitaetsklinikum Ulm AöR

Contact name

Christian Buske

Public contact point

Organisation

Universitaetsklinikum Ulm AöR

Contact name

Christian Buske

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Results and documents

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

Documents 7 files

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

Application history

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