A Phase 2 Clinical Study of CD20×CD3 Bispecific Antibody-Based Salvage Therapy Followed by CAR-T With or Without ASCT in R/R Aggressive B-Cell Lymphoma
This study consists of two sequential treatment phases. In the first phase, patients with r/r aggressive B-NHL receive two cycles of glofitamab ± investigator-selected agents. In the second phase, patients eligible for CAR-T monotherapy undergo FC lymphodepletion followed by CAR-T infusion (2-4×10⁶/kg), while those eligible for CAR-T+ASCT receive conditioning chemotherapy with PBSC reinfusion on day 0 and CAR-T administration (2-4×10⁶/kg) on day +3 (±1). Patients demonstrating Deauville 4-5 or ctDNA positivity at day 28 post-CAR-T infusion subsequently receive four cycles of glofitamab consolidation therapy.
• Patients with relapsed/refractory aggressive B-cell lymphoma, including the following subtypes: diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), or transformed large B-cell lymphoma.
• Relapsed or refractory disease, meeting criteria for one of the following cohorts:
• Cohort 1 (Relapsed/Refractory Disease):
‣ ≥2 prior lines of therapy (including both anti-CD20 monoclonal antibody and anthracycline-based chemotherapy) with documented progression following last treatment; OR
‣ Failure of first-line immunochemotherapy (containing anti-CD20 antibody and anthracycline) defined by any of:
• Relapse/progression within 12 months of treatment completion; OR
∙ Progressive disease during first-line therapy; OR
∙ Stable disease as best response after 4 cycles; OR
∙ Partial response as best response after 6 cycles.
• Cohort 2 (Early Treatment Failure):
⁃ Persistent metabolic activity (Deauville 5) on PET-CT after 2 cycles of first-line immunochemotherapy; OR
⁃ Biopsy-proven residual disease following initial therapy.
• Age ≥18 years and ≤65 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Hematologic parameters at screening must meet the following (unless due to bone marrow involvement):
‣ Absolute neutrophil count (ANC) ≥1×10⁹/L,
⁃ Platelet count (PLT) ≥75×10⁹/L.
• Biochemical parameters at screening must meet the following:
‣ Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN);
⁃ Total bilirubin (TBIL) ≤1.5×ULN (unless due to Gilbert's syndrome or non-hepatic causes);
⁃ Serum creatinine (Cr) ≤2×ULN OR creatinine clearance ≥40 mL/min.
• Left ventricular ejection fraction (LVEF) within institutional normal range by echocardiography.
• Baseline oxygen saturation \>92% on room air.
• Life expectancy ≥3 months as assessed by the investigator.