Epcoritamab in Previously Treated WM

NCT06510491 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 24-121
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

This study is being done to determine if epcoritamab can be used to treat participants with previously treated Waldenstrom Macroglobulinemia (WM). The names of the study drug involved in this study is:

• Epcoritamab (a type of antibody)

Conditions

Waldenstrom Macroglobulinemia; B-Cell Lymphoproliferative Disorder

Keywords

Waldenstrom Macroglobulinemia; B-Cell Lymphoproliferative Disorder

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  The overall response rate (ORR) was defined as the proportion of participants achieving complete response (CR) or partial response (PR) based on modified IWWM6 criteria.

  Up to 12 cycles of treatment (28 days per cycle)

Secondary Outcomes (8)

• 6-month Best Response Rate

  6 months

• Major Response Rate (MRR)

  Up to 12 cycles of treatment (28 days per cycle)

• Median Time to Best Response

  Up to 12 cycles of treatment (28 days per cycle)

• Median Duration of Overall Response (DOR)

  Up to 12 cycles of treatment (28 days per cycle)

• 2-year Progression-Free Survival (PFS) Rate

  2 years

Study Arms (2)

Safety Lead-In Epcoritamab

EXPERIMENTAL

Participants will be enrolled using a modified 3+3 dose-escalation design to establish the Recommended Phase 2 Dose of Epcoritamab and will complete study procedures as follows: * Baseline visit with CT scan and bone marrow biopsy. * Bone marrow biopsy before cycle 6. * Cycles 1 - 3: --Days 1, 8, 15, and 22 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily. * Cycles 4 - 9: --Days 1 and 15 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily. * Cycles 10 - 12: --Day 1 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily. * End of Treatment visit with CT scan and bone marrow biopsy. * Follow up visits: every 3 months for 2 years * Off study visit * If there are 0 out of 3 dose-limiting toxicities (DLTs), the study will proceed to phase II. If 1/3 participants experience a DLT, up to 3 additional participants will be treated at the same dose level. If more than 1/6 total participants experience a DLT, then the study will not proceed to phase 2.

Drug: Epcoritamab

Phase II Epcoritamab

EXPERIMENTAL

Participants will be enrolled and will complete study procedures as follows: * Baseline visit with CT scan and bone marrow biopsy. * Bone marrow biopsy before cycle 6. * Cycles 1 - 3: --Days 1, 8, 15, and 22 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily. * Cycles 4 - 9: --Days 1 and 15 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily. * Cycles 10 - 12: --Day 1 of 28 day cycle: Predetermined dose of Epcoritamab 1x daily. * End of Treatment visit with CT scan and bone marrow biopsy. * Follow up visits: every 3 months for 2 years * Off study visit

Drug: Epcoritamab

Interventions

Epcoritamab DRUG

Bispecific antibody, via subcutaneous (under the skin) injection per protocol.

Also known as: GEN3013, DuoBody-CD3xCD20

Phase II Epcoritamab; Safety Lead-In Epcoritamab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of lymphoplasmacytic lymphoma/WM that is CD20+ by immunophenotype or immunohistochemistry confirmed by bone marrow biopsy/aspirate (fresh or archival tissue acceptable) at time of most recent progression. All degrees of CD20 positivity will be accepted.
• Serum IgM level \>2x upper limit of normal (ULN)
• Meeting criteria for initiation of treatment per IWWM2 criteria \[Kyle Semin Oncol 2002\], including but not limited to hyperviscosity syndrome, peripheral neuropathy, cold agglutinin disease, cryoglobulinemia, amyloidosis, cytopenias due to bone marrow infiltration, symptomatic or bulky lymph nodes, symptomatic splenomegaly, constitutional symptoms not otherwise explained by other causes, signs of organ dysfunction secondary to WM
• At least one prior line of treatment that was discontinued either due to intolerance or disease progression
• Prior therapies must have included an anti-CD20 antibody (e.g. rituximab) and a BTK inhibitor (e.g. ibrutinib, zanubrutinib). Patients who received ibrutinib and rituximab in combination as first line therapy will be eligible. BTKi should be stopped to allow a washout period of no less than 4 half-lives prior to epcoritamab.
• Age ≥18 years
• ECOG performance status £ 2
• Life expectancy of greater than 2 years
• Participants must meet the following organ and marrow function as defined below:
• absolute neutrophil count ≥1000 cells/mcl (G-CSF allowed)
• absolute lymphocyte count ≥200 cells/mcl
• platelets ≥75,000 cells/mcl OR ≥50,000 cells/mcl in the presence of bone marrow involvement or splenomegaly (Note: no PLT transfusions within 7 days prior to screening)
• hemoglobin ≥ 8 g/dL (transfusion allowed)
• total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). In patients with suspected/known Gilbert's disease total bilirubin up to 3x ULN will be allowed but direct bilirubin must be ≤ 2 x ULN
• AST(SGOT)/ALT(SGPT) ≤3× institutional ULN

You may not qualify if:

• Participants who have disease that has transformed to aggressive lymphoma
• Participants with symptomatic or suspected hyperviscosity syndrome or IgM levels greater than 4000 mg/dL who are unable to undergo plasmapheresis to decrease the risk of an IgM flare. Participants who can undergo plasmapheresis will be eligible as long as they undergo the procedure prior to first treatment dose.
• Participants who are receiving any other investigational agent
• Washout from prior therapy: BTKi: no less than5 half-lives prior to epcoritamab to prevent BTKi rebound and rituximab: no less than 4 weeks (28 days) from last dose.
• Participants who have not recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> Grade 1) except for alopecia and peripheral neuropathy
• Uncontrolled intercurrent active infection requiring hospitalization or intravenous antimicrobial agents within 4 weeks of start of treatment
• Uncontrolled underlying cardiac conditions including but not limited to: congestive heart failure grade III or IV (by NYHA) or EF \< 45%, unstable angina pectoris, acute myocardial infarction \< 6 months, uncontrolled cardiac arrhythmia
• History of uncontrolled neurologic condition including but not limited to: seizure disorder, stroke, psychosis, dementia, CNS vasculitis, encephalitis
• Need for supplemental O2 at rest to maintain SaO2\>92%
• Chronic immunosuppressive therapy for non-WM-related indication within 28 days of initiation of treatment, including systemic corticosteroids 20 mg/day or greater prednisone-equivalent
• Patients with known or suspected CNS involvement or leptomeningeal disease (i.e. BingNeel Syndrome) are excluded given concern for potentially increased risk of neurologic toxicity with epcoritamab. Patients with history of CNS malignancy from separate malignancy must have completed CNS-directed therapy and must currently have no evidence of disease
• Pregnant or breastfeeding women or participants unwilling to adhere to institutional guidelines for highly effective contraception for the duration of the therapy are excluded. This is because of the unknown but potential risk of teratogenic or abortifacient effects, as well as potential for adverse events in nursing infants secondary to treatment of the mother, as epcoritamab has not yet been studied in this patient population. A female can be determined to not be of childbearing potential if she meets any of the following criteria:
• Premenarchal
• Postmenopausal (\>45 years of age with amenorrhea for at least 12 months or any age with amenorrhea for at least 6 months and a serum follicle stimulating hormone \[FSH\] level \>40 IU/L or mIU/mL)
• Permanently sterilized (e.g., bilateral tubal occlusion \[which includes tubal ligation procedures as consistent with local regulations\], hysterectomy, bilateral salpingectomy, bilateral oophorectomy) Note: If the childbearing potential changes after start of the trial (e.g., woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) a woman must begin a highly effective method of birth control, as described under 3.1.13.

Sponsors & Collaborators

• Gottfried von Keudell, MD PhD: lead
• Genmab: collaborator

Study Sites (3)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Gottfried von Keudell, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gottfried von Keudell, MD, PhD

CONTACT

617-667-9920; gkeudell@bidmc.harvard.edu

Dea hunsicker, MSN

CONTACT

617-667-9920; dhunsick@bidmc.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: July 15, 2024
• First Posted: July 19, 2024
• Study Start: December 6, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Beth Israel Deaconess Medical Center Technology Ventures Office at tvo@bidmc.harvard.edu

Locations

US (3)