PRIMARY OBJECTIVES:~I. Evaluate the safety and tolerability of loncastuximab tesirine plus mosunetuzumab in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). (Safety Lead-In) II. Estimate the overall response rate (ORR) in R/R DLBCL patients treated with loncastuximab tesirine plus mosunetuzumab. (Phase 2)~SECONDARY OBJECTIVES:~I. Estimate the complete response (CR) rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS) in R/R DLBCL patients treated with loncastuximab tesirine plus mosunetuzumab.~II. Evaluate the toxicity of loncastuximab tesirine plus mosunetuzumab for R/R DLBCL.~EXPLORATROY OBJECTIVE:~I. Evaluate genomic and immune biomarkers of response and resistance to loncastuximab tesirine combined with mosunetuzumab~OUTLINE:~Patients receive loncastuximab tesirine intravenously (IV) and mosunetuzumab IV on study. Patients also undergo positron emission tomography (PET)/computed tomography (CT) scan, biopsy, and collection of blood samples on study.
This phase II trial studies the safety and how well of loncastuximab tesirine when given together with mosunetuzumab works in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or does not respond to treatment (refractory). Loncastuximab tesirine is a monoclonal antibody, loncastuximab, linked to a toxic agent called tesirine. Loncastuximab attaches to anti-CD19 cancer cells in a targeted way and delivers tesirine to kill them. Mosunetuzumab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Giving loncastuximab tesirine with mosunetuzumab may help treat patients with relapsed or refractory diffuse large B-cell lymphoma.