Epcoritamab and Pola-R-mini-CHP for the Treatment of Diffuse Large B Cell Lymphoma in Elderly or Unfit Patients

PRIMARY OBJECTIVE: I. To evaluate whether the addition of epcoritamab to 4- 6 cycles of standard Pola-R-mini-CHP preceded by 2 cycles of epcoritamab monotherapy (E + Pola-mini-CHP) is tolerable and effective. EXPLORATORY OBJECTIVE: I. To include the use of liquid biopsy techniques, specifically PhasED-seq, to assess treatment responses. OUTLINE: CYCLE 1: Patients receive polatuzumab vedotin intravenously (IV) and rituximab IV on day 1 and epcoritamab subcutaneously (SC) on day 1, 8, and 15 of the 21 day cycle, in the absence of disease progression or unacceptable toxicity. CYCLE 2: Patients receive epcoritamab on day 1, 8 and 15 of the 21 day cycle, in the absence of disease progression or unacceptable toxicity. CYCLE 3-4: Patients receive rituximab IV, polatuzumab vedotin IV, cyclophosphamide IV, doxorubicin IV on day 1, epcoritamab SC on days 1, 8 and 15 and prednisone orally (PO) on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients then undergo disease assessment. Patients with complete remission receive cycles 5-6 and patients not in complete remission receive cycles 5-8. CYCLES 5-8: Patients receive rituximab IV, polatuzumab vedotin IV, cyclophosphamide IV, doxorubicin IV and epcoritamab SC on day 1 and prednisone PO on days 1-5 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients undergo urine sample collection and brain magnetic resonance imaging (MRI) during screening and positron emission tomography (PET)/computed tomography (CT) scan and blood sample collection throughout the study. After completion of study treatment, patients are followed up week 36, week 48 then every 12 weeks through week 94, then every 24 weeks through week 240 then every 48 weeks until 6 years after the first dose of treatment. Patients who discontinue for treatment progression are followed up every every 6 months thereafter.