This phase II trial tests how well epcoritamab in combination with standard of care (SOC) platinum-based chemotherapy (rituximab, ifosfamide, carboplatin, etoposide \[RICE\], rituximab, cytarabine, dexamethasone, oxaliplatin or carboplatin RDHAP/X\] or gemcitabine and oxaliplatin \[Gem/Ox\]) and autologous hematopoietic cell transplant (HCT) works in treating patients with large B-cell lymphoma (LBCL) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Epcoritamab, a type of bispecific T-cell engager, 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. Carboplatin is in a class of medications known as platinum-containing compounds. It works in a way similar to the anticancer drug cisplatin, but may be better tolerated than cisplatin. Carboplatin works by killing, stopping or slowing the growth of cancer cells. Oxaliplatin is in a class of medications called platinum-containing antineoplastic agents. It damages the cell's deoxyribonucleic acid (DNA) and may kill cancer cells. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells and some types of cancer cells. This may help the immune system kill cancer cells. Chemotherapy drugs, such as ifosfamide, etoposide phosphate, cytarabine, and gemcitabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. An autologous HCT is a procedure in which blood-forming stem cells (cells from which all blood cells develop) are removed, stored, and later given back to the same person. Giving epcoritamab in combination with SOC platinum-based chemotherapy, such as RICE, RDHAP/X and Gem/Ox, and autologous HCT may kill more cancer cells in patients with relapsed or refractory LBCL.
PRIMARY OBJECTIVE: I. To assess the anti-tumor activity of epcoritamab + platinum-containing chemotherapy + autologous HCT therapy in patients with relapsed or refractory (R/R) LBCL. SECONDARY OBJECTIVES: I. To evaluate the toxicities of epcoritamab + platinum-containing chemotherapy with or without autologous HCT therapy in patients with R/R LBCL. II. To further assess the anti-tumor activity of epcoritamab + platinum-containing chemotherapy + autologous HCT therapy in patients with R/R LBCL. OUTLINE: PRE-AUTOHCT: Patients receive epcoritamab subcutaneously (SC) on days 1, 8, 15, and 22 of each cycle. Cycles repeat every 28 days for up to 3 cycles without disease progression or unacceptable toxicity. Patients may also receive rituximab, cytarabine, dexamethasone, oxaliplatin, or carboplatin once every 21 days for cycles 1-3 or gemcitabine and oxaliplatin once every 2 weeks of each 28-day cycle for cycles 1-3 or rituximab, ifosfamide, carboplatin and etoposide phosphate once every 21 days of cycles 1-3 per SOC. AUTOHCT: Patients undergo autoHCT on week 0 per SOC. POST-AUTOHCT/CONSOLIDATION: Patients receive epcoritamab SC on days 1, 8, 15, and 22 of cycles 1-3, on days 1 and 15 of cycles 4-9, and on day 1 of the remaining cycles. Cycles repeat every 28 days for up to 12 cycles without disease progression or unacceptable toxicity. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening and as clinically indicated, and blood sample collection and computed tomography (CT) or positron emission tomography (PET)/CT throughout the study. Additionally, patients may undergo brain magnetic resonance imaging (MRI) or CT at screening. After completion of study treatment, patients are followed up at 30 days then every 4 months for up to 2 years post autoHCT.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Undergo autoHCT
Given carboplatin
Given cytarabine
Given dexamethasone
Given SC
Given etoposide phosphate
Given gemcitabine
Given ifosfamide
Undergo MUGA
Given oxaliplatin
Given rituximab
University of California Davis Comprehensive Cancer Center
Sacramento, California, United States
RECRUITINGComplete response rate (CRR)
Will be assessed by Lugano 2014. Will be calculated as the number of participants achieving complete response divided by the number of evaluable patients. CRR will be presented alongside the corresponding exact binomial 95% confidence interval.
Time frame: From first dose up to 2 years post-autologous hematopoietic cell transplantation (autoHCT) therapy
Incidence of treatment-related adverse events (AEs)
The proportion of participants experiencing AEs, serious AEs, and treatment delays will be summarized. All AEs will be listed, documenting the course, outcome, severity, and relationship to the study treatment. Incidence rates of AEs and the proportion of participants prematurely withdrawn from the study due to AEs will be reported. Will be classified by severity, and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
Time frame: From first dose through 30 days post last epcoritamab dose
Progression-free survival
Will be summarized using the Kaplan-Meier method. Summary statistics will include median and event-free probabilities at pre-specified time points, along with their associated two-sided 95% confidence intervals (CIs).
Time frame: From the date of enrollment until the first occurrence of disease progression, or death from any cause, whichever occurs first, assessed up to 2 years post-autoHCT therapy
Objective response
Will be assessed by Lugano 2014. Will be presented using descriptive statistics. Tabulations will be produced for appropriate disposition, demographic, baseline, and efficacy parameters. For continuous variables, the number of participants, mean, median, standard deviation, minimum, and maximum values will be presented. For categorical variables, numbers and percentages of participants within each category (with a category for missing data) will be presented along with binomial exact 95% CIs, unless stated otherwise.
Time frame: From first dose up to 2 years post-autoHCT therapy
Overall survival
Will be summarized using the Kaplan-Meier method. Summary statistics will include median and event-free probabilities at pre-specified time points, along with their associated two-sided 95% confidence intervals.
Time frame: From first dose to death due to any causes, assessed up to 2 years post-autoHCT therapy
Duration of minimal residual disease (MRD) negativity
Will be presented using descriptive statistics. Tabulations will be produced for appropriate disposition, demographic, baseline, and efficacy parameters. For continuous variables, the number of participants, mean, median, standard deviation, minimum, and maximum values will be presented. For categorical variables, numbers and percentages of participants within each category (with a category for missing data) will be presented along with binomial exact 95% CIs, unless stated otherwise. Will be calculated by dividing the number of participants with at least one MRD-negative result within 3 cycles of consolidation therapy by the total number of participants who undergo circulating tumor derived deoxyribonucleic acid (ctDNA) MRD testing.
Time frame: Pre-autoHCT and 90 days post-autoHCT
MRD negativity
Will be presented using descriptive statistics. Tabulations will be produced for appropriate disposition, demographic, baseline, and efficacy parameters. For continuous variables, the number of participants, mean, median, standard deviation, minimum, and maximum values will be presented. For categorical variables, numbers and percentages of participants within each category (with a category for missing data) will be presented along with binomial exact 95% CIs, unless stated otherwise. Will be calculated by dividing the number of participants with at least one MRD-negative result within 3 cycles of consolidation therapy by the total number of participants who undergo ctDNA MRD testing.
Time frame: Pre-autoHCT and 90 days post-autoHCT
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.