This is a Phase II, open-label, single-arm, multicenter study designed to evaluate the safety and efficacy of a novel combination therapy-Glofitamab, a PD-1 inhibitor, and Lenalidomide (Glofit-PD-1-Len)-in patients with TP53-aberrant relapsed or refractory large B-cell lymphoma (R/R LBCL). The study will enroll 24 participants and utilize a Simon two-stage design to assess the best complete response rate (BCR), defined as achieving complete remission (CR) per 2014 Lugano criteria during the treatment period. Secondary endpoints include overall response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DoR), and MRD negativity rate at the end of treatment. Safety and tolerability will also be evaluated. This study addresses a critical unmet need for patients with TP53-mutant R/R LBCL, who typically have a poor prognosis under current treatment options.
Signed informed consent form before any study-specific procedures.
Age ≥ 18 years at the time of consent.
Histologically confirmed large B-cell lymphoma (LBCL) with CD20 expression, including but not limited to:Diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS),Transformed follicular lymphoma (tFL),Grade 3B follicular lymphoma (3B FL),High-grade B-cell lymphoma (HGBCL),Intravascular large B-cell lymphoma (IVLBCL),Primary mediastinal large B-cell lymphoma (PMBCL),Epstein-Barr virus-positive LBCL (EBV+ LBCL).
Confirmed TP53 deletion or mutation via FISH or NGS.
Prior allogeneic stem cell transplantation or organ transplantation. Active central nervous system involvement by lymphoma. Active autoimmune diseases requiring immune suppressive therapy. Uncontrolled systemic infections, including active hepatitis B, hepatitis C, or HIV infection.
Single group
Glofitamab
Drugglofitamab is a CD20xCD3 T-cell-engaging bispecific antibody administered intravenously with stepwise dose escalation during the treatment period to reduce the risk of cytokine release syndrome (CRS).
PD-1 Inhibitor
DrugA PD-1 immune checkpoint inhibitor given to enhance T-cell activation and immune-mediated tumor cell killing. Administered according to the study schedule.
Lenalidomide
DrugLenalidomide, an immunomodulatory agent, is administered orally during the treatment cycles to potentiate anti-tumor activity and possibly enhance the activity of both glofitamab and the PD-1 inhibitor.
Obinutuzumab
DrugObinutuzumab, an anti-CD20 monoclonal antibody, is administered intravenously on Day 1 of Cycle 1 as a pretreatment to mitigate immune activation effects and reduce the risk of CRS before starting glofitamab.
Best Complete Response Rate (BCR)
The proportion of participants who achieve a best complete response (CR) during the treatment period, as assessed by the 2014 Lugano criteria using FDG-PET imaging.
Overall Response Rate (ORR)
The proportion of participants who achieve an overall response (complete response or partial response) during the treatment period, as assessed by the 2014 Lugano criteria.
Progression-Free Survival (PFS)
The length of time during and after treatment that the participant lives without progression of the disease, as assessed by 2014 Lugano criteria.
Overall Survival (OS)
The length of time from the start of treatment until death from any cause.
Duration of Response (DoR)
The interval from the initial documentation of response (CR or PR) to the first documentation of disease progression or death.
Minimal Residual Disease (MRD)-Negative Rate
The proportion of patients who achieve minimal residual disease negativity at the completion of treatment.
Transplantation Rate
The proportion of patients who successfully undergo stem cell transplantation after achieving remission with the study treatment.
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