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)
This is an open-label, multicenter, phase II study to evaluate the efficacy and safety of epcoritamab, zanubrutinib, and rituximab (EZR) for participants with relapsed or refractory follicular lymphoma (FL) or marginal zone lymphoma (MZL). The trial will commence with a six participant lead-in cohort for each disease type. The U.S. Food and Drug Administration (FDA) has approved epcoritamab for people who have received at least 2 prior treatments for follicular lymphoma. Epcoritamab is not approved for patients with marginal zone lymphoma. The U.S. FDA has approved zanubrutinib (in combination with a drug called obinutuzumab) for people who have received at least 2 prior treatments for follicular lymphoma. Zanubrutinib is approved for patients with marginal zone lymphoma who have received at lest 1 prior treatment. The FDA has also approved rituximab as a treatment option for follicular lymphoma and marginal zone lymphoma. The research study procedures include screening for eligibility, in-clinic visits, urine tests, blood tests, stool samples, saliva samples, electrocardiograms (ECGs), bone marrow biopsies, Computerized Tomography (CT) scans, Positron Emission Tomography (PET) scans, and questionnaires. Participants will receive study treatment for approximately 12 months and will be followed every 6 months thereafter for up to 10 years. It is expected that about 45 people will take part in this research study (24 FL participants and 21 MZL participants). Genmab is supporting this research study by providing the study drug, epcoritamab, and funding for the study. BeOne Medicines, Inc. is supporting this research study by providing the study drug, zanubrutinib, and funding for the study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
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.
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
RECRUITINGMemorial Sloan Kettering Cancer Center
New York, New York, United States
RECRUITINGComplete 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.
Time frame: 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.
Time frame: 6 months
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.
Time frame: 12 months
Partial Response Rate (PRR)
PRR is defined as the participants who achieved partial response during study. Response is defined using Lugano criteria.
Time frame: 12 months
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.
Time frame: 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)
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.
Time frame: 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)
EOT CRR is defined as the proportion of participants who achieved complete response (CR) at the end of treatment visit. Response is assessed by PET/CT using Lugano criteria.
Time frame: 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.
Duration of Response (DOR)
The duration of overall response is measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started, or death due to any cause). Participants without events reported are censored at the last disease evaluation.
Time frame: 5 years
Duration of Complete Response (DOCR)
The duration of overall CR is measured from the time measurement criteria are first met for CR until the first date that progressive disease is objectively documented, or death due to any cause. Participants without events reported are censored at the last disease evaluation.
Time frame: 5 years
2-Year Progression Free Survival (PFS2)
2-year PFS is the percent probability estimate at 2 years based on the Kaplan-Meier method. PFS is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD are censored at the earliest of the date of the last disease evaluation or start of new anti-cancer therapy.
Time frame: 2 years
Median Progression Free Survival
PFS based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Participants alive without PD are censored at the earliest of the date of the last disease evaluation or start of new anti-cancer therapy.
Time frame: 5 years
Median Time-to-next treatment (TTNT)
Time to next treatment (TTNT) based on Kaplan-Meier methodology will be calculated as time from the start of treatment to the date of initiation of the next line of treatment. Participants who have not progressed to a subsequent line of therapy, will be censored at the date of last follow up or at death.
Time frame: 5 years
Median Overall Survival (OS)
OS based on Kaplan-Meier methodology is defined as the time from registration to death due to any cause, or censored at date last known alive.
Time frame: 12 years
Incidence of Histological Transformation
Incidence of Histological Transformation (HT) based on Kaplan-Meier methodology defined as as the number of cases of HT divided by the total number of individuals in the population at risk at that specific time interval.
Time frame: 5 years
Cytokine Release Syndrome (CRS) Rate
CRS Rate is defined as the proportion of participants who experience CRS. CRS is graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) grading.
Time frame: 12 months
Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) Rate
ICANS Rate is defined as the proportion of participants who experienced ICANS during the study. ICANS graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) grading.
Time frame: 12 months
Rate of Grade 3 or Higher Toxicity Regardless of Attribution
The percentage of participants who experience a maximum grade 3 or higher adverse event based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms.
Time frame: 12 months
Rate of Grade 2 or Higher Toxicity at Least Possibly Related to Study Treatment
The percentage of participants who experience a maximum grade 2 or higher at least possibly related to study treatment adverse event based on the Common Toxicity Criteria for Adverse events Version 5.0 (CTCAEv5) as reported on case report forms.
Time frame: 12 months
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