A Phase 2 interventional study of Glofitamab and PD-1 Inhibitor in Large B-cell Lymphoma and TP53, sponsored by The First Affiliated Hospital with Nanjing Medical University. Recruiting at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-11-20.
Sponsored by The First Affiliated Hospital with Nanjing Medical University · Phase 2, Interventional, and Treatment
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.
This is a Phase II, open-label, single-arm, multicenter study designed to evaluate the safety and efficacy of the Glofitamab-PD-1 inhibitor-Lenalidomide combination therapy (Glofit-PD-1-Len) in patients with TP53-aberrant relapsed or refractory large B-cell lymphoma (R/R LBCL). The study aims to investigate whether this novel therapeutic combination can effectively address the high unmet medical need in this patient population, characterized by poor prognosis and resistance to standard treatments.
The study employs a Simon two-stage design, enrolling a total of 24 participants. In Stage I, an initial cohort of 9 patients will be treated and evaluated. If fewer than 2 patients achieve complete response (CR) per 2014 Lugano criteria (as verified by FDG-PET imaging), the study will be terminated early. If the threshold is met, an additional 15 patients will be recruited in Stage II for further evaluation, bringing the total to 24 patients. The primary endpoint is the best complete response rate (BCR) achieved during the treatment cycle. Secondary endpoints include overall response rate (ORR), progression-free survival (PFS), overall survival (OS), duration of response (DoR), duration of complete remission (DoCR), transplantation rate, and minimal residual disease (MRD)-negative rate at the end of treatment.
The treatment process consists of an induction stage following a screening period of up to 28 days. On Day 1 of the first treatment cycle, patients will receive pretreatment with Obinutuzumab, followed by Glofitamab with stepwise dose escalation, combined with the PD-1 inhibitor and Lenalidomide. Efficacy assessments will occur at predefined time points using Lugano response criteria. The safety of the Glofit-PD-1-Len regimen will be closely monitored, and adverse events will be recorded and graded per CTCAE version 5.0.
Patients will be excluded if they meet criteria such as prior organ transplant, recent exposure to other investigational treatments, or significant comorbid conditions, including active infections and uncontrolled autoimmune diseases. Concomitant therapies, such as corticosteroids (except for specific indications), experimental therapies, and live vaccines, are prohibited. Prophylactic measures for tumor lysis syndrome (TLS), nausea, vomiting, and diarrhea, as well as granulocyte colony-stimulating factor (G-CSF) support, will be implemented as per institutional guidelines.
The risk-benefit profile of this combination is supported by prior studies demonstrating the efficacy and acceptable safety of Glofitamab in combination therapies for LBCL. Given the significant treatment gap for TP53-aberrant R/R LBCL patients, this research seeks to advance outcomes through an innovative therapeutic approach.
The First Affiliated Hospital with Nanjing Medical University is the lead sponsor of 543 studies on the registry; 301 are open to participants now.
Counted across the registry records on this site, refreshed daily.
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.
One lymph node lesion ≥ 1.5 cm (in the longest diameter), or One extranodal lesion ≥ 1.0 cm (in the longest diameter).
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 Criteria:
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.
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.
Drug: Glofitamab · Drug: PD-1 Inhibitor · Drug: Lenalidomide · Drug: Obinutuzumab
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).
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, 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, 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.
Time frame: Up to 18 months after the first dose
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.
Time frame: Up to 18 months after the first dose
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.
Time frame: Time from the first dose to disease progression or death, assessed up to 24 months
Overall Survival (OS)
The length of time from the start of treatment until death from any cause.
Time frame: Time from the first dose to death from any cause, assessed up to 24 months
Duration of Response (DoR)
The interval from the initial documentation of response (CR or PR) to the first documentation of disease progression or death.
Time frame: From the date response is first documented to the date of disease progression or death, up to 24 months
Duration of Complete Remission (DoCR)
The interval from the initial documentation of CR to the first documentation of disease progression or death.
Time frame: From the date complete response (CR) is first documented to the date of disease progression or death, up to 24 months
Incidence of Treatment-Related Adverse Events (Safety and Tolerability)
The incidence, type, and severity of adverse events (graded according to CTCAE v5.0), and their relationship to the study treatment.
Time frame: Up to 24 months
Minimal Residual Disease (MRD)-Negative Rate
The proportion of patients who achieve minimal residual disease negativity at the completion of treatment.
Time frame: At the end of treatment, approximately 20 months
Transplantation Rate
The proportion of patients who successfully undergo stem cell transplantation after achieving remission with the study treatment.
Time frame: Up to 12 months after the first dose
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The First Affiliated Hospital with Nanjing Medical University