Relapsed/Refractory Diffuse Large B Cell Lymphoma

This is a Phase III randomized, double-blind, positive controlled study to evaluate the efficacy, safety, and pharmacokinetics of HMPL-760 in combination with R-GemOx versus placebo in combination with R-GemOx in patients with R/R DLBCL.

In this study, researchers are looking to determine whether Gemcitabine/Oxaliplatin plus a lower dose of Epcoritamab (12 mg) works to treat subjects with relapsed/refractory diffuse large B-cell lymphoma, who are candidates to autologous stem cell transplantation.

The goal of this clinical trial is to evaluate the efficacy and safety of early secondary infusion of CD19 CAR T-cell therapy in adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), guided by ctDNA monitoring. The main questions it aims to answer are: 1. Efficacy: Does early secondary CAR-T infusion improve the 3-month complete remission (CR) rate and long-term survival outcomes (e.g., 1-year PFS, OS)? 2. Safety: What are the adverse events associated with secondary CAR-T infusion, such as cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity (ICANS), and infections? This is a single-arm, single-center, prospective study. All participants will receive: * Leukapheresis to collect T cells for CAR-T manufacturing. * Preconditioning chemotherapy (fludarabine and cyclophosphamide) to prepare the body for CAR-T infusion. * Two CD19 CAR-T infusions: The first infusion (2×10⁶ cells/kg) followed by a second infusion (same dose) if ctDNA remains positive when PET/CT shows CR or PET/CT shows PR within 60 days post-first infusion. Participants will undergo: * Frequent hospital monitoring for ≥14 days post-infusion to manage potential toxicities. * Regular follow-ups (e.g., blood tests, ctDNA analysis, PET/CT scans) at scheduled intervals up to 12 months. * Continuous safety assessments, including CRS grading, neurological evaluations, and infection monitoring.

This is a multicenter, randomized, controlled, open-label Phase III clinical trial, aimed at evaluating the efficacy and safety of BEBT-908 combined with rituximab (R) compared to investigator-selected standard chemotherapy regimens \[Standard of Care (SOC)\] \[i.e., rituximab-gemcitabine-oxaliplatin (R-GemOx) or rituximab-ifosfamide-carboplatin-etoposide (R-ICE)\] for the treatment of relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL).