Epco, Zanu, Ritux for R/R FL or MZL
A Phase 2 Study of Epcoritamab, Zanubrutinib, and Rituximab (EZR) for Treatment of Relapsed or Refractory Follicular Lymphoma or Marginal Zone Lymphoma
1 other identifier
interventional
45
1 country
3
Brief Summary
The purpose of this study is to determine how effective and safe the combination of epcoritamab, zanubrutinib, and rituximab is in treating participants with relapse or refractory Follicular Lymphoma (FL) or marginal zone lymphoma (MZL).
- The names of the study drugs involved in this research study are:
- Epcoritamab (a type of antibody)
- Zanubrutinib (a type of Bruton tyrosine kinase inhibitor)
- Rituximab (a type of monoclonal antibody)
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Jan 2025
Longer than P75 for phase_2
3 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 19, 2024
CompletedFirst Posted
Study publicly available on registry
August 21, 2024
CompletedStudy Start
First participant enrolled
January 21, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2030
February 19, 2026
February 1, 2026
3.1 years
August 19, 2024
February 17, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Complete Metabolic Response (CMR) Rate among patients with R/R FL
CMR rate is defined as the proportion of participants who achieved CMR during study. CMR assessed by PET/CT is defined using Lugano criteria.
6 months
Complete Metabolic Response (CMR) Rate among patients with R/R MZL
CMR rate is defined as the proportion of participants who achieved CMR during study. CMR assessed by PET/CT or CT is defined using Lugano criteria.
6 months
Secondary Outcomes (16)
Objective Response Rate (ORR)
12 months
Partial Response Rate (PRR)
12 months
End-of-treatment Objective Response Rate (EOT ORR)
Up to 12 months - End-of treatment visit occurs 4 weeks after cycle 12 day 1. Each cycle is 4 weeks. Participants who discontinue therapy due to toxicity would also undergo an EOT evaluation approximately 4 weeks after the last dose of study treatment.
End-of-treatment Partial Response Rate (EOT PRR)
Up to 12 months - End-of treatment visit occurs 4 weeks after cycle 12 day 1. Each cycle is 4 weeks. Participants who discontinue therapy due to toxicity would also undergo an EOT evaluation approximately 4 weeks after the last dose of study treatment.
End-of-treatment Complete Response Rate (EOT CRR)
Up to 12 months - End-of treatment visit occurs 4 weeks after cycle 12 day 1. Each cycle is 4 weeks. Participants who discontinue therapy due to toxicity would also undergo an EOT evaluation approximately 4 weeks after the last dose of study treatment.
- +11 more secondary outcomes
Study Arms (2)
Rituxan + Zanubrutinib + Epcoritamab for FL
EXPERIMENTALEnrolled participants will complete: * Baseline visit with imaging and bone marrow biopsy * Imaging on cycles 3, 6, 9 * Up to 1 year of treatment with study drugs * End of Treatment visit with imaging and bone marrow biopsy * Follow up visits every 6 months for up to 10 years
Rituxan + Zanubrutinib + Epcoritamab for MZL
EXPERIMENTALEnrolled participants will complete: * Baseline visit with imaging and bone marrow biopsy * Imaging on cycles 3, 6, 9 * Up to 1 year of treatment with study drugs * End of Treatment visit with imaging and bone marrow biopsy * Follow up visits every 6 months for up to 10 years
Interventions
Bruton tyrosine kinase inhibitor, 80 mg immediate-release capsule, taken orally per protocol.
Chimeric anti-CD20 monoclonal antibody, 10 or 50 mL single-use vials, via intravenous infusion per institutional standard.
Bispecific antibody, 5 or 60 mg/mL vials, via subcutaneous (under the skin) injection per protocol.
Eligibility Criteria
You may qualify if:
- Histologically confirmed diagnosis of CD20+ FL (grade 1-3A) or CD20+ MZL (any subtype) (at time of trial entry) with review of the diagnostic pathology specimen at one of the participating institutions. Patients with current histologic transformation are excluded.
- Receipt of at least one prior line of therapy for FL or MZL (with prior treatment including a CD20 monoclonal antibody).
- Measurable disease, defined as ≥1 measurable nodal lesion (long axis \>1.5 cm or short axis \>1.0 cm), or ≥1 measurable extra-nodal lesion (long axis \>1.0 cm), or spleen \>13 cm on PET, CT, or magnetic resonance imaging (MRI). For patients with FL, disease should be FDG-avid based on PET. FDG-avid disease is NOT a requirement for patients with MZL.
- Meets at least one criterion to begin treatment based on the modified GELF (Groupe d'Etude des Lymphomes Folliculaires) criteria:
- Symptomatic adenopathy
- Organ function impairment due to disease involvement, including cytopenias due to marrow involvement (WBC \<1.5x109/L; absolute neutrophil count \[ANC\] \<1.0x109/L, Hgb \<10g/dL; or platelets \<100x109/L)
- Constitutional symptoms (defined as persistent fevers \>100.4 F, shaking chills, drenching night sweats, or loss of \>10% of body weight within 6 months)
- Any nodal or extranodal tumor mass \>7 cm in maximum diameter
- \>3 nodal sites of involvement \>3 cm
- Local compressive symptoms or imminent risk thereof
- Splenomegaly (craniocaudal diameter \> 16cm on CT imaging)
- Clinically significant pleural or peritoneal effusion
- Leukemic phase (\>5x109/L circulating malignant cells)
- Rapid generalized disease progression
- Renal infiltration
- +15 more criteria
You may not qualify if:
- Patients who require systemic immunosuppressive therapy for an ongoing medical condition will be excluded. For corticosteroids, patients receiving a prednisone dose of \>10 mg daily (or equivalent) will not be eligible. A short course of steroids (up to 14 days) for lymphoma-related symptom palliation or for prophylaxis (i.e., IV contrast allergy) is allowed, in which case patients should be off steroids prior to treatment start.
- Patients with bulky cervical adenopathy that is compressing the upper airway or could result in significant airway compression during a tumor flare event.
- Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia).
- Presence of HCV antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable (NOTE: the limit of detection for HCV RNA must have a sensitivity of \< 15 IU/mL). Subjects who received treatment for HCV that was intended to eradicate the virus and who have an undetectable HCV RNA may participate without serial HCV RNA screening. Other patients may participate if they are willing to undergo every 3-month monitoring for HCV reactivation.
- Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with positive hepatitis B serologies with undetectable HBV DNA (NOTE: the limit of detection for HBV DNA must have a sensitivity of \< 20 IU/mL) are permitted in the trial but should receive prophylactic antiviral therapy (i.e. entecavir) and undergo every 3 month HBV DNA monitoring.
- Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) requiring antimicrobial therapy at trial enrolment or significant infections within 2 weeks of study treatment initiation.
- Subject has a known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection or has had recent known exposure to someone with SARS-CoV-2 infection, the subject must have a negative molecular (e.g., PCR) test, or 2 negative antigen test results at least 24 hours apart, to rule out SARS-CoV-2 infection. Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and may only rescreen after they meet the following SARS-CoV-2 infection viral clearance criteria:
- No signs/symptoms suggestive of active SARS-CoV-2 infection
- Negative molecular (e.g., PCR) result or 2 negative antigen test results at least 24 hours apart
- Prior history of another malignancy (except for non-melanoma skin cancer, in situ cervical or breast cancer, or Gleason 6 prostate cancer managed with observation) unless disease free for at least 2 years OR unless the likelihood of relapse is very low in the opinion of the treating physician.
- Patients should not have received immunization with attenuated live vaccine within one week of study entry or during study period. Vaccination with live vaccines within 28 days of the first dose of study treatment is prohibited.
- Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study or limit adherence to study requirements.
- Patients with any one of the following currently on or in the previous 6 months will be excluded: myocardial infarction, congenital long QT syndrome, torsade de pointes, unstable angina, coronary/peripheral artery bypass graft, cardiac arrhythmia (CTCAE grade 3 or higher), or cerebrovascular accident. History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place. Uncontrolled hypertension as indicated by ≥ 2 consecutive blood pressure measurements showing systolic blood pressure \> 170 mm Hg and diastolic blood pressure \> 105 mm Hg at screening.
- Patients with 1) New York Heart Association Class III or IV heart failure or known ejection fraction of \<45%, 2) MI within 6 months prior to screening, 3) unstable angina within 3 months before screening, or 4) history of clinically significant arrhythmias within 6 months of screening (eg sustained Vtach, Vfib, torsades de pointes).
- Inability to comply with protocol mandated restrictions.
- +20 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Reid Merryman, MDlead
- BeiGenecollaborator
- Genmabcollaborator
Study Sites (3)
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10021, United States
The Ohio State University Wexner Medical Center
Columbus, Ohio, 43210, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Reid Merryman, MD
Dana-Farber Cancer Institute
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Sponsor Investigator
Study Record Dates
First Submitted
August 19, 2024
First Posted
August 21, 2024
Study Start
January 21, 2025
Primary Completion (Estimated)
March 1, 2028
Study Completion (Estimated)
March 1, 2030
Last Updated
February 19, 2026
Record last verified: 2026-02
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 Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.