This phase Ib trial tests the safety and effectiveness of epcoritamab in treating patients with post-transplant lymphoproliferative disorder (PTLD) that has come back after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Epcoritamab, a bispecific antibody, binds to a protein called CD3, which is found on T cells (a type of white blood cell). It also binds to a protein called CD20, which is found on B cells (another type of white blood cell) and some lymphoma cells. This may help the immune system kill cancer cells. Giving epcoritamab may be safe and effective in treating patients with relapsed or refractory B-cell PTLD.
PRIMARY OBJECTIVE: I. To assess the safety of treatment with epcoritamab in subjects with PTLD. SECONDARY OBJECTIVES: I. To estimate the Objective Response Rate (ORR), defined as the clinical response (complete response \[CR\] + partial response \[PR\]) after 3 cycles of epcoritamab. II. To estimate the clinical benefit rate (CBR) in subjects with PTLD treated with epcoritamab. III. To estimate the best objective response rate (BOR) in subjects with PTLD treated with epcoritamab. IV. To estimate the progression free survival (PFS) in subjects with PTLD treated with epcoritamab. V. To estimate the duration of complete response (DoCR) in subjects with PTLD treated with epcoritamab. VI. To estimate the overall survival (OS) in subjects with PTLD treated with epcoritamab. EXPLORATORY OBJECTIVES: I. To characterize the peripheral immunophenotype changes through the course of treatment with epcoritamab in subjects with PTLD. II. To describe the relationship of tumor microenvironment characteristics with clinical response to epcoritamab in subjects with PTLD. III. To characterize Epstein-Barr virus (EBV) methylation alterations in EBV positive PTLDs treated with epcoritamab IV. To describe the relationship between metabolic tumor volume and response to epcoritamab in subjects with PTLD. OUTLINE: This is a dose-escalation study of epcoritamab followed by a dose-expansion study. Patients receive epcoritamab subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 4-9, and day 1 of each subsequent cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with CR may continue to receive epcoritamab if disease progression occurs within 6 months. Patients with PR or stable disease (SD) continue to receive epcoritamab in the absence of disease progression or unacceptable toxicity. Patients also undergo positron emission tomography (PET)/computed tomography (CT) and blood sample collection throughout the study and may undergo biopsy during screening. After completion of study treatment, patients are followed up at 28 days and then every 3 months for up to 3 years.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Undergo biopsy
Undergo blood sample collection
Undergo PET/CT
Given SC
Undergo PET/CT
Washington University
St Louis, Missouri, United States
RECRUITINGOhio State University Comprehensive Cancer Center
Columbus, Ohio, United States
RECRUITINGIncidence of adverse events
Will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) grading for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). The dose limiting toxicity period will be the first 28 days after the first dose of epcoritamab.
Time frame: Up to 30 days after the last dose of the study drug
Objective response rate (ORR)
Will be defined as the number of patients who achieve complete response (CR) + partial response (PR) divided by the number of evaluable patients, and presented with the 95% binomial confidence interval. Will be assessed using Lugano (with LYRIC modification) response criteria.
Time frame: Up to completion of cycle 3 (1 cycle = 28 days)
Clinical benefit rate (CBR)
Will be defined as clinical response (CR + PR + stable disease) after 6 cycles of epcoritamab using Lugano (with LYRIC modification) response criteria. CBR rate will be estimated and 95% confidence interval computed.
Time frame: Up to 6 cycles (1 cycle = 28 days)
Best Overall Response Rate (ORR)
Will be defined as the number of patients who achieve best ORR (CR + PR) at any time after treatment with epcoritamab. Will be estimated with the 95% binomial confidence interval. Will be assessed using Lugano (with LYRIC modification) response criteria.
Time frame: Up to 3 years
Progression free survival
Will be estimated using the Kaplan-Meier method. Will be assessed using the LYRIC response criteria.
Time frame: From the date of treatment initiation to date of progression or death, whichever occurs first, assessed up to 3 years
Duration of complete response
Will be estimated using the Kaplan-Meier method. Will be assessed using the LYRIC response criteria.
Time frame: From treatment response to date of progression or death, whichever occurs first, assessed up to 3 years
Overall survival
Will be estimated using the Kaplan-Meier method.
Time frame: From date of treatment initiation to date of death due to all causes, assessed up to 3 years
The Ohio State University Comprehensive Cancer Center
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