Epcoritamab and Tazemetostat for the Treatment of Relapsed or Refractory Grade I-IIIa Follicular Lymphoma

NCT06575686 | Suspended Phase 2 DMC FDA Drug

• 3 other identifiers: 23820NCI-2024-06708P30CA033572
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial tests the safety, side effects and effectiveness of epcoritamab and tazemetostat in treating patients with grade I-IIIa follicular lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Epcoritamab is a bispecific monoclonal antibody that binds to two different antigens on the surface of cancer cells that may help the body's immune system attack the cancer and may interfere with the ability of the cancer cells to grow and spread. Tazemetostat, a EZH2 inhibitor, may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving epcoritamab and tazemetostat may be safe, tolerable and/or effective in treating patients with relapsed or refractory grade I-IIIa follicular lymphoma.

Conditions

Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3a Follicular Lymphoma; Refractory Grade 1 Follicular Lymphoma; Refractory Grade 2 Follicular Lymphoma; Refractory Grade 3a Follicular Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence of unacceptable adverse events (Safety lead-in)

  Observed toxicities will be summarized by type, severity, and attribution. (each cycle is 28 days)

  up to first 2 cycles of study treatment

• Complete response (CR) rate

  CR rate will be defined as a best response of CR according to Lugano criteria before any documented disease progression or any subsequent non-Hodgkin lymphoma (NHL) treatment. CR rate will be estimated along with the 95% exact binomial confidence interval.

  Up to 3 years

Secondary Outcomes (5)

• Overall response rate (ORR)

  Up to 3 years

• Duration of response (DOR)

  From CR or PR to disease progression/relapse or death, up to 3 years

• Progression-free survival (PFS)

  From start of protocol treatment to disease relapse/progression or death, up to 3 years

• Overall survival (OS)

  From start of protocol treatment to death, up to 3 years

• Incidence of adverse events

  Up to 60 days after last dose of study drug

Study Arms (1)

Treatment (epcoritamab, tazemetostat)

EXPERIMENTAL

Patients receive tazemetostat PO BID on days 1-28 of each cycle. Patients also receive epcoritamab SC on days 1, 8, 15, and 22 of cycles 2-4 then on day 1 of remaining cycles. Cycles repeat every 28 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood samples on study and undergo bone marrow biopsy and CT or PET/CT throughout the study.

Procedure: Biospecimen Collection; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Biological: Epcoritamab; Procedure: Positron Emission Tomography; Drug: Tazemetostat

Interventions

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Treatment (epcoritamab, tazemetostat)

Computed Tomography PROCEDURE

Undergo CT or PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, tomography

Treatment (epcoritamab, tazemetostat)

Epcoritamab BIOLOGICAL

Given SC

Also known as: Anti-CD20/CD3 Bispecific Antibody GEN3013, DuoBody-CD3xCD20, Epcoritamab-bysp, Epkinly, GEN 3013, GEN-3013, GEN3013, Tepkinly

Treatment (epcoritamab, tazemetostat)

Positron Emission Tomography PROCEDURE

Undergo PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Treatment (epcoritamab, tazemetostat)

Tazemetostat DRUG

Given PO

Also known as: E 7438, E-7438, E7438, EPZ 6438, EPZ-6438, EPZ6438

Treatment (epcoritamab, tazemetostat)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (epcoritamab, tazemetostat)

Eligibility Criteria

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

You may qualify if:

• Documented informed consent of the participant and/or legally authorized representative
• Assent, when appropriate, will be obtained per institutional guidelines
• Agreement to allow the use of archival tissue from diagnostic tumor biopsies
• If unavailable, exceptions may be granted with study principal investigator (PI) approval
• Age: ≥ 18 years
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Histologically confirmed follicular lymphoma, grades 1-3A
• Relapsed/ refractory disease after at least one line of prior lymphoma therapy
• Radiologically measurable lymphadenopathy (≥ 1.5 cm) or ≥ 1 measurable extranodal lesion (long axis \> 1.0 cm) on CT scan or magnetic resonance imaging (MRI)
• Fully recovered from the acute toxic effects (except alopecia) to ≤ grade 1 to prior anti-cancer therapy
• WITHOUT BONE MARROW INVOLVEMENT: Absolute neutrophil count (ANC) ≥ 1,000/mm\^3 (NOTE: Growth factor use is allowed to reach ANC)
• WITH BONE MARROW INVOLVEMENT: ANC ≥ 500/mm\^3 (NOTE: Growth factor use is allowed to reach ANC)
• WITHOUT BONE MARROW INVOLVEMENT: Platelets ≥ 50,000/mm\^3 (NOTE: Platelet transfusions are within 14 days of platelet assessment if thrombocytopenia is secondary to disease involvement)
• WITH BONE MARROW INVOLVEMENT: Platelets ≥ 25,000/mm\^3 (NOTE: Platelet transfusions are within 14 days of platelet assessment if thrombocytopenia is secondary to disease involvement)
• Total bilirubin ≤ 2 x upper limit of normal (ULN) (unless has Gilbert's disease or secondary to disease)

You may not qualify if:

• Concurrent enrollment in another therapeutic investigational study
• Prior bispecific antibodies or tazemetostat
• Autologous stem cell transplant within 30 days prior to day 1 of protocol therapy
• Allogeneic stem cell transplant if complicated by active graft versus host disease (GVHD) or if on immunosuppressive agents
• Chemotherapy, radiation therapy, biological therapy, immunotherapy within 21 days or five half-lives (whichever is shorter for non-radiation therapy) prior to day 1 of protocol therapy
• Immunosuppressive agents other than prednisolone 20 mg daily or equivalent
• Major surgery within 4 weeks of first dose of study drug
• Vaccination with live vaccines within 4 weeks of the first dose of study drug
• Strong and moderate CYP3A4 inducers/ inhibitors within 14 days prior to day 1 of protocol therapy
• Current evidence of central nervous system involvement by the lymphoma
• Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia, or NYHA (New York Heart Association) heart failure class III-IV, or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months of screening
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
• History of active human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV)
• Participants who are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded
• Known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection

Sponsors & Collaborators

• City of Hope Medical Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

City of Hope Medical Center

Duarte, California, 91010, United States

Location

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Specimen Handling; Biopsy; Magnetic Resonance Spectroscopy; tazemetostat

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)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Swetha Kambhampati

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2024
• First Posted: August 28, 2024
• Study Start: March 11, 2025
• Primary Completion (Estimated): July 16, 2028
• Study Completion (Estimated): July 16, 2028
• Last Updated: January 21, 2026

Record last verified: 2026-01

Locations

US (2)