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)
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.
Symptomatic adenopathy
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.
Parallel
Zanubrutinib
DrugBruton tyrosine kinase inhibitor, 80 mg immediate-release capsule, taken orally per protocol.
Rituximab
DrugChimeric anti-CD20 monoclonal antibody, 10 or 50 mL single-use vials, via intravenous infusion per institutional standard.
Epcoritamab
DrugBispecific antibody, 5 or 60 mg/mL vials, via subcutaneous (under the skin) injection per protocol.
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.
Complete Response (CR) 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.
Objective Response Rate (ORR)
ORR is defined as the participants who achieved complete response (CR) and partial response (PR) during study. Response is defined using Lugano criteria.
Partial Response Rate (PRR)
PRR is defined as the participants who achieved partial response during study. Response is defined using Lugano criteria.
End-of-treatment Objective Response Rate (EOT ORR)
EOT ORR is defined as the proportion of participants who achieved complete response (CR) or partial response (PR) at the end of treatment visit. Response is assessed by PET/CT using Lugano criteria.
End-of-treatment Partial Response Rate (EOT PRR)
EOT PRR is defined as the proportion of participants who achieved partial response (PR) at the end of treatment visit. Response is assessed by PET/CT using Lugano criteria.
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Reid Merryman, MD
Lead sponsor
Dana-Farber Cancer Institute
Sponsor institution
BeiGene
Collaborator
Genmab
Collaborator
