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Epcoritamab with Lenalidomide and Tafasitamab for the treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma, The ECLAT Trial
Trial Status: active
This phase II trial studies how well epcoritamab with lenalidomide and tafasitamab work in treating patients with diffuse large B-cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Epcoritamab is a bispecific antibody. Antibodies are proteins made by the immune system to fight infections and other possible harms to the body. A bispecific antibody is developed in the laboratory to bind to two different proteins. Epcoritamab can bind to specific proteins on two different types of white blood cells called B and T cells. These cells help the body fight cancers and infections. One side of epcoritamab attaches to a protein called CD3 on T cells. The other side of epcoritamab attaches to a protein called CD20 on normal healthy and cancerous B cells. By connecting at the same time to CD3 and CD20, epcoritamab brings T cells and B cells close together and directs the T cells to kill the B cells, including the cancerous B cells. This helps kill cancer cells. Lenalidomide is a drug that works against cancer cells by helping to change or control the functioning of the immune system. Tafasitamab is a monoclonal antibody that blocks a protein in the body that can cause tumors to grow. Monoclonal antibodies target and destroy only certain cells in the body. This selective targeting may help protect healthy cells from damage. It targets the CD19 antigen which are expressed on the surface of B-cells, which then signals the immune system’s natural killer cells to destroy those B-cells, which helps the body’s immune system target the cancer cells and destroy them. Giving the combination of epcoritamab with lenalidomide and tafasitamab may be an effective treatment for patients with relapsed/refractory diffuse large B-cell lymphoma.
Inclusion Criteria
Age ≥ 18 years
Pathologically confirmed diffuse large B cell lymphoma, transformed indolent lymphoma, primary mediastinal B cell lymphoma, high grade B cell lymphoma, follicular lymphoma grade 3B
Subjects must have histologically confirmed CD20+ lymphoma and documented in the most recent representative pathology report
Presence of CD19 is not required to be confirmed (except if patients have received anti-CD19 therapy in the past). Patients treated with prior anti-CD19 therapy must have confirmation of CD19 expression in a biopsy done after progression on the last CD19 directed therapy
At least 2 prior lines of systemic therapy including chimeric antigen receptor T-cell therapy (CART) or autologous stem cell transplant (ASCT) (up to 4 prior lines of therapy allowed). Note that bridging therapy prior to ASCT or CART will be counted as a separate line of therapy)
At least one prior line of systemic therapy for patients ineligible for ASCT/CART or patients unwilling to undergo CAR-T/ASCT for logistic or other reasons (up to 4 prior lines of therapy allowed)
Have radiologically measurable lymphadenopathy or extranodal involvement
Eastern Cooperative Oncology Group performance status (PS) ≤ 2 (ECOG > 2 can be enrolled if PS compromised from lymphoma e.g. spinal cord compression and expected to improve rapidly with therapy)
Hemoglobin ≥ 8 g/dL (red blood cell transfusions are allowed)
Absolute neutrophil count (ANC) ≥ 1,000/mm^3 or ≥ 500/mm^3 if due to disease involvement in the bone marrow (granulocyte colony-stimulating factor [G-CSF] use is allowed)
Platelet count ≥ 75,000 cells/mm^3 or ≥ 50,000/mm^3 if due to disease involvement in the bone marrow (platelets transfusions are allowed)
Estimated creatinine clearance (CrCl) ≥ 40 mL/min (Cockcroft-Gault formula or other institutional standard methods)
Serum aspartate transaminase (AST) or alanine transaminase (ALT) ≤ 2.5 x upper limit of normal (ULN)
Direct bilirubin ≤ 2 x ULN (≤ 3 if due to Gilbert's syndrome or liver involvement by the lymphoma)
Negative HIV test at screening, with the following exception: Individuals with a positive HIV test at screening are eligible provided, prior to enrollment, they are stable on antiretroviral therapy for at least 1 year, have a CD4 count ≥ 200/µL, and have an undetectable viral load
Signed informed consent form(s)
Ability to comply with all the study-related procedures, in the investigator’s judgement
Subject is willing to take aspirin prophylaxis (subjects with low or intermediate risk for thromboembolism) or prophylactic anticoagulant (if high risk for a thromboembolic event)
Contraception requirements
* Patient is willing to adhere to pregnancy risk minimization plan associated with lenalidomide treatment
* For all females of child-bearing potential; a negative serum pregnancy test (beta-human chorionic gonadotropin [hCG]) at the screening visit and a negative serum or urine pregnancy test at baseline prior to the first dose of study drug
* Female subjects of childbearing potential must practice at least 2 protocol-specified methods of birth control, that are effective from 30 days prior to treatment through at least 12 months after the last dose of study drug
* Female subjects of non-childbearing potential do not need to use birth control
* Female who is not pregnant, breastfeeding, donating eggs (ova, oocytes), or considering
* Becoming pregnant during the study or for 12 months after the last dose of study drug
* If male, and subject is sexually active with female partner(s) of childbearing potential, he must agree, from 30 days prior to treatment initiation through 12 months after the last dose of study drug, to practice the protocol-specified contraception
* Male who is not considering fathering a child or donating sperm during the study or for 12 months after the last dose of study drug
Coronavirus disease 2019 (COVID19) eligibility criteria: Patient should have no known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. If a patient has signs/symptoms suggestive of SARS-CoV-2 infection or have had recent known exposure to someone with SARS-CoV-2 infection, the subject must have a negative molecular (e.g., polymerase chain reaction [PCR]) test, or 2 negative antigen test results at least 24 hours apart, to rule out SARS-CoV-2 infection. * Note: SARS-CoV-2 diagnostic tests should be applied following local requirements/recommendations
Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and may only rescreen after they meet the following SARS-CoV-2 infection viral clearance criteria:
* No signs/symptoms suggestive of active SARS-CoV-2 infection
* Negative molecular (e.g., PCR) result or 2 negative antigen test results at least 24 hours apart
Exclusion Criteria
Prior CD3/CD20 bispecific antibody (BiAb) based therapy (Patients who received prior CD3/CD20 BiAb as part of frontline therapy for DLBCL and were in remission for at least 1 year post frontline therapy are allowed)
Prior tafasitamab and/or lenalidomide therapy for lymphoma (Patients who received prior tafasitamab and/or lenalidomide as part of frontline therapy for DLBCL and were in remission for at least 1 year post frontline therapy are allowed)
Active central nervous system (CNS) involvement (previously treated CNS lymphoma is permissible)
Active secondary malignancy
* Patients who have a concurrent malignancy that is clinically stable and does not require tumor-directed treatment is allowed e.g., low grade prostate cancer under surveillance
* Patients with a previously treated malignancy should be eligible to participate if all treatment of that malignancy was completed at least 2 years before registration and the patient has no evidence of disease
Uncontrolled HIV or active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (controlled HIV with undetectable viral load, previously treated HBV and HCV are allowed if HBV DNA and HCV ribonucleic acid [RNA] are negative respectively, hepatitis B core antibody [HBcAb] positive with hepatitis B surface antigen [HBsAg] negative disease is permitted if patient is willing to take entecavir prophylaxis)
Known active or latent tuberculosis
Prior solid organ transplantation
Prior allogeneic stem cell transplantation
Uncontrolled active systemic infection
Major surgery within 4 weeks of the first dose of study drug (exceptions may be allowed after discussion with principal investigator [PI] if patient has fully recovered from procedure and anti-lymphoma therapy is urgently needed)
Known clinically significant cardiovascular disease, including:
* Onset of unstable angina pectoris within 6 months of signing informed consent form (ICF)
* Acute myocardial infarction within 6 months of signing ICF
* Congestive heart failure (grade III or IV as classified by the New York Heart Association and/or known decrease ejection fraction of < 45%)
* Stroke or intracranial hemorrhage within 6 months prior to signing ICF
** In case of any other history of major cardiovascular disease, a cardiology consult is required within 60 days of enrollment
Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator’s opinion, could compromise the subject’s safety or risk study outcomes
Vaccination with live vaccines within 28 days prior to enrollment
Additional locations may be listed on ClinicalTrials.gov for NCT07030699.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Memorial Sloan Kettering Basking Ridge
Status: Active
Contact: Pallawi Torka
Phone: 201-775-7808
Middletown
Memorial Sloan Kettering Monmouth
Status: Active
Contact: Pallawi Torka
Phone: 201-775-7808
Montvale
Memorial Sloan Kettering Bergen
Status: Active
Contact: Pallawi Torka
Phone: 201-775-7808
New York
Commack
Memorial Sloan Kettering Commack
Status: Active
Contact: Pallawi Torka
Phone: 201-775-7808
New York
Memorial Sloan Kettering Cancer Center
Status: Active
Contact: Pallawi Torka
Phone: 201-775-7808
Uniondale
Memorial Sloan Kettering Nassau
Status: Active
Contact: Pallawi Torka
Phone: 201-775-7808
West Harrison
Memorial Sloan Kettering Westchester
Status: Active
Contact: Pallawi Torka
Phone: 201-775-7808
PRIMARY OBJECTIVE:
I. Evaluate efficacy [best complete response rate (CRR)] of epcoritamab with lenalidomide and tafasitamab (epco-tafa-len) in patients with relapsed/refractory (RR) diffuse large B-cell lymphoma (DLBCL).
SECONDARY OBJECTIVES:
I. Evaluate secondary measures of efficacy: Best overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), duration of complete response (DOCR), event-free survival (EFS), and overall survival.
II. Characterize the adverse event profile of the combination.
EXPLORATORY OBJECTIVES:
I. Evaluate additional measures of efficacy such as CRR and ORR at the end of therapy, 1-year PFS and overall survival (OS) and 2-year PFS and OS.
II. To characterize response to epco-tafa-len regimen based on cell of origin and DLBCL subtypes by gene expression profiling (GEP).
III. To understand the circulating tumor deoxyribonucleic acid (ctDNA) response kinetics of the combination.
OUTLINE:
Patients receive epcoritamab subcutaneously (SC) on days 1, 8, 15, and 22 of cycles 1-3 and on day 1 of cycles 4-12, tafasitamab intravenously (IV) over 1.5 to 2.5 hours on days 1, 8, 15, and 21 of cycles 1-3 and on days 1 and 15 of cycles 4-12, and lenalidomide orally (PO) once daily (QD) on days 1-21 of each cycle. Cycles repeat every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection and positron emission tomography/computed tomography (PET/CT), CT, and/or magnetic resonance imaging (MRI) scans throughout the study. Patients may also undergo bone marrow aspiration and biopsy during screening.
After completion of study treatment, patients are followed every 3 months.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center