Phase 2 Study of Epcoritamab in Combination With Loncastuximab Tesirine in Relapsed/Refractory Large B-cell Lymphoma
The purpose of this study is to determine whether combining Loncastuximab Tesirine with Epcoritamab is tolerable and effective for reducing and/or eliminating lymphoma cells in the body.
• Men and women aged 18 years or older at the time of signing informed consent.
• Able and willing to sign the informed consent form (ICF).
• Ability to comply with the trial protocol.
• Relapsed/refractory (r/r) large B-cell lymphoma (LBCL) as determined by the local hematopathology laboratory from the following diagnoses by 2016 World Health Organization (WHO) classification of lymphoid neoplasms (Swerdlow et al., 2016):
∙ LBCL or DLBCL, not otherwise specified (NOS)
‣ High-grade B-cell lymphoma (NOS or double/triple hit \[technically classified in WHO 2016 as high-grade B-cell lymphoma (HGBCL), with Myc and B-cell lymphoma 2 (BCL2) and/or B-cell lymphoma 6 (BCL6) translocations\])
‣ Transformed from follicular lymphoma, marginal zone lymphoma (MZL), and nodular lymphocyte predominant Hodgkin lymphoma
‣ Follicular lymphoma stage 3B
‣ Primary mediastinal B-cell lymphoma previously treated with checkpoint inhibitor Note: Relapsed disease is defined as disease that has recurred ≥6 months after completion of therapy. Refractory disease is defined as disease that either progressed during therapy or progressed within 6 months (\<6 months) of completion of therapy.
• Participants who have received at least one prior systemic therapy for LBCL including anti-cluster of differentiation 20 (anti-CD20) monoclonal antibody and anthracycline-containing therapy.
• Measurable disease by 2014 Lugano Classification. (Participants who have measurable disease, defined as at least 1 bi-dimensionally measurable nodal lesion, defined as \>1.5 cm in its longest dimension, or at least 1 bi-dimensionally measurable extra nodal lesion, defined as \>1.0 cm in its longest dimension.)
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2.
• Adequate hematologic, hepatic, and renal function tested within 6 weeks prior to the start of therapy (values must not be achieved with growth factors within 72 hs):
∙ Absolute neutrophil count (ANC) ≥ 1.0 × 10\^9 cells/L
‣ Hemoglobin ≥8.0 g/dL without blood transfusion in the past week
‣ Platelet count ≥75 × 10\^9 platelets/L or ≥ 50 × 10\^9 platelets/L if bone marrow involvement or splenomegaly
‣ Total bilirubin ≤1.5 × upper limit normal (ULN). Participants with documented history of Gilbert's syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible (≤3x institutional ULN if lymphoma involvement of the liver).
‣ Alanine transaminase (ALT)/aspartate aminotransferase (AST) ≤3.0 × ULN or ≤5 × ULN in the presence of liver involvement by lymphoma.
• i. Creatinine within normal institutional limits, or calculated creatinine clearance ≥40 mL/min by the Cockcroft-Gault Equation or other institutional standard methods
• Willingness to avoid pregnancy during the trial and for at least 12 months after the last dose of the trial intervention.
⁃ Patients with history of human immunodeficiency virus (HIV) are eligible, provided they are stable on anti-retroviral therapy, have cluster of differentiation 4 (CD4) count ≥200/µL, and have an undetectable viral load. Note: HIV test is optional.
⁃ Life expectancy of at least 12 weeks
⁃ For patients receiving glucocorticoid treatment at screening: treatment must be tapered down and administered with a maximum of 25 mg daily in the last 14 days before the first dose of epcoritamab.