The Efficacy and Safety of Glofitamab in Combination With PD-1 Antibody and Lenalidomide in Patients With Relapsed/Refractory Large B-cell Lymphoma (LBCL) With TP53 Aberrations: A Prospective, Multicenter, Phase II Clinical Study

Sponsor
The First Affiliated Hospital with Nanjing Medical University
Study ID
NCT07240194
Phase
PHASE2
Status
Recruiting
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Conditions

  • Large B-cell Lymphoma
  • TP53

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Glofitamab — DRUG
    glofitamab 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 — DRUG
    A PD-1 immune checkpoint inhibitor given to enhance T-cell activation and immune-mediated tumor cell killing. Administered according to the study schedule.
  • Lenalidomide — DRUG
    Lenalidomide, 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 — DRUG
    Obinutuzumab, 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.

Study Details

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.

Key Dates

Start date
Sep 1, 2025
Status verified
Nov 2025
Primary completion
Dec 30, 2028
Completion
Dec 30, 2028

Study Design

Enrollment
24 participants (estimated)
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT

Arms

  • Experimental: Glofitamab + PD-1 Inhibitor + Lenalidomide
    This arm involves a single-arm experimental treatment where participants receive a combination therapy of glofitamab (administered with stepwise dose escalation), a PD-1 inhibitor, and Lenalidomide. The regimen is designed for participants with TP53-aberrant relapsed or refractory large B-cell lymphoma (R/R LBCL). Obinutuzumab may be administered on Day 1 of the first treatment cycle for pretreatment.

Primary Outcome Measure

Best Complete Response Rate (BCR) [ Time Frame: Up to 18 months after the first dose ]

Central Contacts

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