HOVON 178 WM: Treatment of Waldenstrom’s macroglobulinemia with epcoritamab if the disease comes back during or after previous treatment

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Decision date (initial)

2026-03-10

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: Safety, Pharmacokinetic, Pharmacogenetic, Efficacy, Therapy, Pharmacodynamic

Phase Ib: To establish the recommended phase II dose (RP2D) for epcoritamab in patients with R/R WM,
Phase II: To evaluate the preliminary efficacy of epcoritamab after 12 cycles in R/R WM patients in terms of major response rate (defined as complete remisson (CR), very good partial response (VGPR) or partial

Secondary objectives 7

1. Phase Ib: To evaluate safety and tolerability of epcoritamab treatment in patients with R/R WM
2. Phase II: To evaluate the efficacy of epcoritamab in terms of overall response rate (ORR) and categorical responses (PD, SD, MR, PR, VGPR, CR) including best response on protocol, categorical responses after 12 cycles and 24 cycles.
3. Phase II: To evaluate the efficacy of epcoritamab in terms of progression free survival (PFS), overall survival (OS), and treatment-free survival (TFS)
4. Phase II: To evaluate the efficicacy of epcoritamab in terms of time to next treatment (TTNT), time on treatment (TOT), time to response, time to best response and duration of response (DOR)
5. Phase II: To evaluate the quality of life (QoL)
6. Phase II: To evaluate the safety and tolerability
7. Phase II: To evaluate the incidence, severity, and type of infections

Conditions and MedDRA coding

relapsed or refractory Waldenstrom’s macroglobulinemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. Diagnosed with WM, according to criteria in appendix ‎A
2. Age ≥ 18 years
3. Indication for therapy based on IWMM consensus criteria (see appendix ‎A)
4. Relapsed or refractory WM
5. 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)
6. Measurable disease (IgM M-protein > 5 g/L or, in case M-protein is present but unquantifiable, total serum IgM level > 10 g/L)
7. BM LPL infiltrate positive for CD20 at screening
8. Acceptable Complete Blood Count (CBC), renal function, liver function and coagulation status, defined as per the following laboratory measurements: o Hemoglobin (Hb) > 5.6 mmol/L or Hb > 9 g/dL (unless related to WM) o Estimated creatinin clearance > 45 mL/min (Cockroft-Gault) o Serum ALT ≤ 3.0 upper limit of normal (ULN) o Serum AST ≤ 3.0  ULN o Total billirubin ≤ 1.5 x ULN (unless attributable to Gilbert’s syndrome or controlled autoimmune hemolytic anemia) o Absolute 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 Platelet count > 30 x109/L unless trombopenia is due to BM involvement of WM in which case the minimum is > 10 x 109/L o Prothrombin Time (PT), International Normalized Ratio (INR), and Activated Partial Thromboplastin Time (aPTT) ≤ 1.5 x ULN (unless receiving anticoagulation)
9. ECOG/WHO performance status ≤ 2 (see appendix ‎D)
10. 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.
11. Negative pregnancy test at study entry for women of childbearing potential
12. 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
13. Patient is capable of giving informed consent
14. Written informed consent

Exclusion criteria 25

1. Large cell transformation, central nervous system (CNS) involvement/Bing Neel Syndrome and/or AL (Amyloid Light-Chain) Amyloidosis
2. Peripheral neuropathy of CTCAE grade ≥ 3
3. Recent WM treatment: o For chemotherapy and/or rituximab and/or bortezomib and/or other proteasome inhibitors: within 4 weeks prior to first epcoritamab dose. o For BTK-inhibitors (monotherapy): within 14 days, prior to the first dose of epcoritamab o For autoSCT (autologous stem cell transplantation): 100 days prior to first epcoritimab dose. o For 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
4. Prior solid organ or allogeneic hematopoietic stem cell transplantation (prior autoSCT is acceptable)
5. Prior treatment with a CD3 × CD20 bispecific antibody
6. 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.
7. History of drug-specific hypersensitivity or anaphylaxis to any study drug (including active product or excipient components)
8. Active bleeding or uncontrolled severe bleeding diathesis (e.g., hemophilia or severe von Willebrand disease)
9. 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
10. Has suspected active or inadequately treated latent tuberculosis
11. 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)
12. Severe pulmonary dysfunction (CTCAE grade III-IV, see appendix ‎F‎)
13. Severe neurological dysfunction including psychiatric disease CTCAE grade III-IV (see appendix ‎F)
14. Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, cancer, etc.)
15. History of active malignancy (other than inclusion diagnosis) with the exception of: o Non-invasive basal cell or squamous cell skin carcinoma o Cervical carcinoma, stage 1B or less o Non-invasive, superficial bladder cancer o Prostate cancer with a current PSA level < 0.1 ng/mL o Any curable cancer with a CR of > 2 years duration
16. 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.
17. Patients with an active HBV and/or HCV infection.
18. Patients with symptomatic IgG or IgA or non-secreting LPL
19. Uncontrolled hyperviscosity syndrome and/or Plasmapheresis < 35 days prior to screening and/or initiation of study drug
20. Vaccination with live attenuated vaccines within 28 days prior to registration
21. Major surgery within 28 days prior to registration
22. Breastfeeding or pregnant female patients
23. Current participation in another clinical trial with medicinal products
24. Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
25. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the patient

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase Ib: RP2D for epcoritamab based on incidence of DLTs
2. Phase II: Major response rate (defined as CR, VGPR or PR) after 12 cycles of epcoritamab

Secondary endpoints 10

1. Phase II: Duration of response (DOR), defined as time from first response to progressive disease (PD) or death from any cause
2. Phase II: Time to response, time to best response and best response on protocol
3. Phase II: Categorical response rates (PD, SD, MR, PR, VGPR, CR) after 12 and after 24 cycles of epcoritamab
4. 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
5. Phase II: Time on treatment (TOT), defined as time from first epcoritamab dose to last administration of epcoritamab
6. Phase II: Overall survival (OS), defined as the time from start epcoritamab to death from any cause
7. Phase II: Time to next treatment (TTNT), defined as time from start epcoritamab to next line of WM treatment.
8. 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
9. 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)
10. Phase II: Health-related quality of life (QoL) by EORTC QLQ-C30

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Sponsor organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Address

Dr. Molewaterplein 40

City

Rotterdam

Postcode

3015 GD

Country

Netherlands

Scientific contact point

Organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Contact name

Dr. J.M.I. Vos

Public contact point

Organisation

Hemato-Oncologie voor Volwassenen Nederland (Hovon) Stichting

Contact name

HOVON

Third parties 5

Locations

3 EU/EEA countries · 7 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 28 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