RecruitingPhase 2NCT07240194

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

Enrollment

24 participants

Start Date

Sep 1, 2025

Study Type

INTERVENTIONAL

Conditions

TP53 Large B-cell Lymphoma

Summary

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria15

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).
Relapsed or refractory (R/R) LBCL defined as:
Relapsed: Disease recurrence after achieving remission for longer than 6 months after completing the last line of therapy.
Refractory: Failure to achieve remission or progression within 6 months after completing the last line of therapy.
Confirmed TP53 deletion or mutation via FISH or NGS.
Not eligible for autologous stem cell transplantation (ASCT) per any of the following criteria: Age ≥ 70 years, End-stage organ dysfunction, ECOG performance status of ≥ 2,Patient decision to decline ASCT, Other investigator-determined comorbidities (e.g., severe heart or lung disease, active infections) per local clinical practice standards.
Measurable disease at baseline, with at least:
One lymph node lesion ≥ 1.5 cm (in the longest diameter), or One extranodal lesion ≥ 1.0 cm (in the longest diameter).
ECOG performance status of 0, 1, or 2.
Life expectancy of ≥ 12 weeks, as assessed by the investigator.
Adequate hematologic function unless due to extensive bone marrow involvement or spleen-related complications caused by lymphoma, defined as:
Absolute neutrophil count (ANC) ≥ 1.0 × 10⁹/L,Platelets ≥ 50 × 10⁹/L,Hemoglobin ≥ 80 g/L.
Willingness to adhere to the study procedures, including contraception requirements during the trial for participants of reproductive potential.

Exclusion Criteria5

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.
Previous treatment with Glofitamab, another bispecific antibody targeting CD20 and CD3, or PD-1 inhibitors combined with Lenalidomide.
History of severe hypersensitivity to monoclonal antibodies or any components of the study drugs.
Concurrent participation in another investigational study. Use of systemic immunosuppressive therapy within 14 days prior to enrollment (excluding corticosteroids for lymphoma treatment or prevention of adverse effects).
Pregnant or breastfeeding women. Any psychological, social, or medical condition that, in the investigator's opinion, could interfere with study compliance or compromise the participants' safety or outcome.

Interventions

DRUGGlofitamab

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).

DRUGPD-1 Inhibitor

A PD-1 immune checkpoint inhibitor given to enhance T-cell activation and immune-mediated tumor cell killing. Administered according to the study schedule.

DRUGLenalidomide

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.

DRUGObinutuzumab

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.