Epcoritamab and Rituximab for First-line Follicular Lymphoma

NCT05783609 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-702
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to determine how effective and safe the combination of rituximab and epcoritamab is in treating patients with Follicular Lymphoma (FL) and who have not received other treatments for their lymphoma. The names of the study drugs involved in this study are:

• Rituximab (a type of monoclonal antibody therapy)
• Epcoritamab (a T-cell bispecific antibody)

Conditions

Follicular Lymphoma; Low Grade Non-Hodgkin's Lymphoma, Adult

Keywords

Immunotherapy; Follicular Lymphoma; Low-grade Non-Hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

• End of Treatment (EOT) Complete Metabolic Response (CMR) Rate

  EOT CMR rate defined as the proportion of participants achieving CR per PET/CT Lugano 2014 criteria (protocol appendix B) at the EOT assessment: PET-CT, score 1, 2, or 3 with or without a residual mass on a 5-point scale (5PS) among all patients and separately in Cohorts A and B.

  (Cycle 1 = 36 days, cycle 2-9 = 28 days), up to 267 days

Secondary Outcomes (17)

• Best Partial Metabolic Response (PMR) Rate

  (Cycle 1 = 36 days, cycle 2-9 = 28 days), up to 267 days

• Best Objective Metabolic Response (OMR) Rate

  (Cycle 1 = 36 days, cycle 2-9 = 28 days), up to 267 days

• EOT Partial Metabolic Response (PMR) Rate

  (Cycle 1 = 36 days, cycle 2-9 = 28 days), up to 267 days

• EOT Objective Metabolic Response (OMR) Rate

  (Cycle 1 = 36 days, cycle 2-9 = 28 days), up to 267 days

• 2-year Duration of Response (DOR)

  2 years

Study Arms (2)

Epcoritamab + Rituximab

EXPERIMENTAL

Participants will undergo study procedures as outlined: * PET/CT scans at baseline and after cycles 2, 5, and 9 of treatment. * Cycle 1: * Days -14, -7, 1, 8 of 6 week cycle: Predetermined dose of Rituximab. * Days 1, 8, 15, 22 of 6 week cycle: Predetermined dose of Epcoritamab. (Day 15 of Epcoritamab dosage will be administered in the hospital.) * Cycles 2 - 3: --Days 1, 8, 15, 22 of 4 week cycle: Predetermined dose of Epcoritamab. * Cycles 4 - 9: * Day 1 of 4 week cycle: Predetermined dose of Epcoritamab. * Day 15 of 4 week cycle: Predetermined dose of Epcoritamab. * Surveillance imaging (PT/CT scans) at months 13, 18, and 24 after initiation of treatment. * Follow up visits for up to 5 years.

Drug: Epcoritamab; Drug: Rituximab

Epcoritamab + Rituximab Expansion

EXPERIMENTAL

Participants will undergo study procedures as outlined: * PET/CT scans at baseline and after cycles 2, 5, and 9 of treatment. * Cycle 1: * Days -14, -7, 1, 8 of 6 week cycle: Predetermined dose of Rituximab. * Days 1, 8, 15, 22 of 6 week cycle: Predetermined dose of Epcoritamab. * Cycles 2 - 3: --Days 1, 8, 15, 22 of 4 week cycle: Predetermined dose of Epcoritamab. * Cycles 4 - 9: * Day 1 of 4 week cycle: Predetermined dose of Epcoritamab. * Surveillance imaging (PT/CT scans) at months 13, 18, and 24 after initiation of treatment. * Follow up visits for up to 5 years.

Drug: Epcoritamab; Drug: Rituximab

Interventions

Epcoritamab DRUG

T-cell bispecific antibody, via subcutaneous injection

Also known as: DuoBody-CD3xCD20, GEN3013

Epcoritamab + Rituximab; Epcoritamab + Rituximab Expansion

Rituximab DRUG

Chimeric anti-CD20 monoclonal antibody, via IV infusion

Also known as: Rituxan, MabThera

Epcoritamab + Rituximab; Epcoritamab + Rituximab Expansion

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of CD20+ FL (grade 1-3A) with review of the diagnostic pathology specimen at one of the participating institutions. Patients with current or prior histologic transformation are excluded.
• No prior systemic therapy for FL. Prior treatment with radiation therapy or short course steroids is allowed.
• 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 a 6 month period)
• 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
• Bone lesions

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 symptom palliation 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 with stage I follicular lymphoma
• Patients who are candidates for radiation therapy with curative intent (in the opinion of the treating investigator)
• 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).
• Active HBV (DNA PCR-positive) or hepatitis C (RNA PCR-positive infection). Subjects with evidence of prior HBV but who are PCR-negative are permitted in the trial but should receive prophylactic antiviral therapy. Subjects who received treatment for HCV that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable.
• Known history of seropositivity for human immunodeficiency virus (HIV). Note: HIV testing is required at screening only if required per local health authorities or institutional standards.
• Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at trial enrolment or significant infections within 2 weeks prior to the first dose of epcoritamab.
• Prior history of another malignancy (except for non-melanoma skin cancer or in situ cervical or breast cancer) unless disease free for at least 2 years.
• Patients should not have received immunization with attenuated live vaccine within one week of study entry or during study period.
• 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), clinically significant ECG abnormalities, or cerebrovascular accident.
• Patients with New York Heart Association Class III or IV heart failure or known ejection fraction of \<45%.
• Inability to comply with protocol mandated hospitalizations and restrictions.
• Patients who are pregnant, breast-feeding, or intending to become pregnant during the study.

Sponsors & Collaborators

• Reid Merryman, MD: lead
• Genmab: collaborator
• AbbVie: collaborator

Study Sites (5)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

University of Rochester Medical Center

Rochester, New York, 14642, United States

RECRUITING

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Reid Merryman, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Reid Merryman, MD

CONTACT

617-632-3352; reid_merryman@dfci.harvard.edu

Heather A Walker, MPH

CONTACT

857-215-1833; heathera_walker@dfci.harvard.edu

Study Design

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

Study Record Dates

• First Submitted: March 13, 2023
• First Posted: March 24, 2023
• Study Start: June 21, 2023
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2030
• Last Updated: December 23, 2025

Record last verified: 2025-12

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

Locations

US (5)