EPCORITAMAB for Relapsed or refractory Waldenstrom macroglobulinemia | Waldenstrom macroglobulinemia

Inclusion criteria

• {"criterion_text":"- Diagnosed with WM, according to criteria in appendix ‎A\n- Negative serological testing for hepatitis B virus (HBV) (Hepatitis B surface antigen (HBsAg) negative and hepatitis B core antibody (anti-HBc) negative) and hepatitis C virus (hepatitis C antibody). Patients who are positive for anti-HBc or hepatitis C antibody may be included if they have a negative PCR within 6 weeks before enrollment. Those who are PCR positive will be excluded.\n- Negative pregnancy test at study entry for women of childbearing potential\n- Agreement to use adequate contraception during the trial and for 4 months after last epcoritamab administration, for women of childbearing potential or men sexually active with a woman of childbearing potential\n- Patient is capable of giving informed consent\n- Written informed consent\n- Age ≥ 18 years\n- Indication for therapy based on IWMM consensus criteria (see appendix ‎A)\n- Relapsed or refractory WM\n- At least 1 prior line of systemic therapy for WM (including at least: either a BTK-inhibitor or an anti-CD20 antibody combined with chemotherapy)\n- Measurable disease (IgM M-protein > 5 g/L or, in case M-protein is present but unquantifiable, total serum IgM level > 10 g/L)\n- BM LPL infiltrate positive for CD20 at screening\n- Acceptable Complete Blood Count (CBC), renal function, liver function and coagulation status, defined as per the following laboratory measurements: o\tHemoglobin (Hb) > 5.6 mmol/L or Hb > 9 g/dL (unless related to WM) o\tEstimated creatinin clearance > 45 mL/min (Cockroft-Gault) o\tSerum ALT ≤ 3.0 upper limit of normal (ULN) o\tSerum AST ≤ 3.0  ULN o\tTotal billirubin ≤ 1.5 x ULN (unless attributable to Gilbert’s syndrome or controlled autoimmune hemolytic anemia) o\tAbsolute neutrophil count (ANC) > 1.0 x 109/L, unless neutropenia is due to BM involvement of WM in which case the minimum is > 0.5 x 109/L o\tPlatelet count > 30 x109/L unless trombopenia is due to BM involvement of WM in which case the minimum is > 10 x 109/L o\tProthrombin Time (PT), International Normalized Ratio (INR), and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN (unless receiving anticoagulation)\n- ECOG/WHO performance status ≤ 2 (see appendix ‎D)"}

Exclusion criteria

• {"criterion_text":"- Large cell transformation, central nervous system (CNS) involvement/Bing Neel Syndrome and/or AL (Amyloid Light-Chain) Amyloidosis\n- Has suspected active or inadequately treated latent tuberculosis\n- Severe cardiovascular disease (New York Heart Association (NYHA) classification III-IV; see appendix G) (arrhythmias requiring chronic treatment, congestive heart failure or symptomatic ischemic heart disease)\n- Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix ‎F‎)\n- Severe neurological dysfunction including psychiatric disease CTCAE grade III-IV (see appendix ‎F)\n- Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.)\n- History of active malignancy (other than inclusion diagnosis) with the exception of: o\tNon-invasive basal cell or squamous cell skin carcinoma o\tCervical carcinoma, stage 1B or less o\tNon-invasive, superficial bladder cancer o\tProstate cancer with a current PSA level < 0.1 ng/mL o\tAny curable cancer with a CR of > 2 years duration\n- Uncontrolled HIV infection. Patients with HIV positivity but with viral suppression (VL< lower limit of detection) and CD4 count > 350 for over 1 year, no history of AIDS-defining illnesses with the exception of lymphoma diagnosis may be enrolled.\n- Patients with an active HBV and/or HCV infection.\n- Patients with symptomatic IgG or IgA or non-secreting LPL\n- Uncontrolled hyperviscosity syndrome and/or Plasmapheresis < 35 days prior to screening and/or initiation of study drug\n- Peripheral neuropathy of CTCAE grade ≥ 3\n- Vaccination with live attenuated vaccines within 28 days prior to registration\n- Major surgery within 28 days prior to registration\n- Breastfeeding or pregnant female patients\n- Current participation in another clinical trial with medicinal products\n- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule\n- Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient\n- Recent WM treatment: o\tFor chemotherapy and/or rituximab and/or bortezomib and/or other proteasome inhibitors: within 4 weeks prior to first epcoritamab dose. o\tFor BTK-inhibitors (monotherapy): within 14 days, prior to the first dose of epcoritamab o\tFor autoSCT (autologous stem cell transplantation): 100 days prior to first epcoritimab dose. o\tFor any other treatment and/or investigational drug: 4 weeks or 5 half-lives prior to first epcoritamab dose, whichever is longer, prior to the planned first dose of epcoritamab\n- Prior solid organ or allogeneic hematopoietic stem cell transplantation (prior autoSCT is acceptable)\n- Prior treatment with a CD3 × CD20 bispecific antibody\n- Autoimmune disease or other diseases that require permanent or high-dose immunosuppressive therapy, including indication for systemic cortisteroids at > 10 mg daily prednisone or equivalent.\n- History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components)\n- Active bleeding or uncontrolled severe bleeding diathesis (e.g., hemophilia or severe von Willebrand disease)\n- Ongoing active bacterial, viral, fungal, mycobacterial, parasitic or other infection requiring systemic treatment (excluding prophylactic treatment) at the time of enrollment or within the previous 2 weeks prior to the planned first dose of trial drug, including COVID-19 infection. Note that a past COVID-19 infection may be a risk factor, but if resolved and the subject is vaccinated, it may be allowable to enroll the subject"}

Primary endpoints

• {"endpoint_text":"- Phase Ib: RP2D for epcoritamab based on incidence of DLTs\n- Phase II: Major response rate (defined as CR, VGPR or PR) after 12 cycles of epcoritamab","definition_or_measurement_approach":"Phase Ib: based on incidence of dose limiting toxicities (DLTs). Phase II: Major response rate defined as CR (complete remission), VGPR (very good partial response) or PR (partial response) after 12 cycles of epcoritamab."}

Secondary endpoints

• {"endpoint_text":"- Phase II: Duration of response (DOR), defined as time from first response to progressive disease (PD) or death from any cause\n- Phase II: Time to response, time to best response and best response on protocol\n- Phase II: Categorical response rates (PD, SD, MR, PR, VGPR, CR) after 12 and after 24 cycles of epcoritamab\n- Phase II: Progression-free survival (PFS), defined as time from start epcoritamab to the first occurrence of disease progression or death from any cause, whichever occurs first\n- Phase II: Time on treatment (TOT), defined as time from first epcoritamab dose to last administration of epcoritamab\n- Phase II: Overall survival (OS), defined as the time from start epcoritamab to death from any cause\n- Phase II: Time to next treatment (TTNT), defined as time from start epcoritamab to next line of WM treatment.\n- Phase II: Treatment free survival (TFS), defined as time from date of last protocol treatment to date start of next (new) line of treatment, or death from any cause, whichever comes first\n- Phase II: Safety parameters: Type, frequency, and severity of- adverse events (AEs) and- AEs of special interest (AESI) and their relationship to study treatment (determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0)\n- Phase II: Health-related quality of life (QoL) by EORTC QLQ-C30","definition_or_measurement_approach":"Definitions provided in endpoints: DOR = time from first response to PD or death; PFS = time from start to progression or death; TOT = time from first to last dose; OS = time from start to death; TTNT = time from start to next WM treatment; TFS = time from last protocol treatment to start of next treatment or death; Safety per NCI CTCAE v5.0; QoL measured by EORTC QLQ-C30."}

Belgium

Earliest CTIS Part Ii Submission Date

10-02-2026

Latest Decision Or Authorization Date

10-03-2026

Processing Time Days

28

Number Of Sites

2

Number Of Participants

5

Netherlands

Earliest CTIS Part Ii Submission Date

12-02-2026

Latest Decision Or Authorization Date

16-03-2026

Processing Time Days

32

Number Of Sites

3

Number Of Participants

14

Denmark

Earliest CTIS Part Ii Submission Date

03-03-2026

Latest Decision Or Authorization Date

28-04-2026

Processing Time Days

56

Number Of Sites

2

Number Of Participants

9

Primary sponsor

Full Name

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Organisation Type

Patient organisation/association

Country Of Registered Address

Netherlands

Third parties

• {"country":"Germany","full_name":"AbbVie Biotechnology GmbH","duties_or_roles":"Providing IMP","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"Clinigen Clinical Supplies Management","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"Denmark","full_name":"GCP-enheden ved Københavns Universitetshospital","duties_or_roles":"","organisation_type":"Health care"}
• {"country":"Netherlands","full_name":"IKNL","duties_or_roles":"On site datamanagement","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"Amsterdam UMC Stichting","duties_or_roles":"Biobanking","organisation_type":"Patient organisation/association"}