Glofitamab plus PD‑1 antibody and lenalidomide for relapsed/refractory TP53‑aberrant large B‑cell lymphoma

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

This trial will test whether combining glofitamab with a PD‑1 antibody and lenalidomide can help adults with relapsed or refractory large B‑cell lymphoma that has TP53 mutations or deletions.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The First Affiliated Hospital with Nanjing Medical University (Academic / other)
• Drugs / interventions: Glofitamab, Obinutuzumab
• Locations: 1 site (Nanjing, Jiangsu)
• Trial ID: NCT07240194 on ClinicalTrials.gov

What this trial studies

This is a single‑arm, open‑label Phase II trial giving glofitamab, a PD‑1 antibody, and lenalidomide to adults with relapsed or refractory CD20‑positive large B‑cell lymphoma and confirmed TP53 aberrations. The study uses a Simon two‑stage design with an initial cohort of 9 patients and a planned total enrollment of 24 if early efficacy thresholds are met. The primary endpoint is best complete response rate per 2014 Lugano criteria by FDG‑PET, and secondary endpoints include overall response rate, progression‑free survival, overall survival, duration of response, MRD negativity, and safety/tolerability. Treatment includes an induction period with premedication and scheduled imaging and labs to monitor response and adverse events.

Who should consider this trial

Good fit: Adults (≥18) with relapsed or refractory CD20‑positive large B‑cell lymphoma and confirmed TP53 mutation or deletion who are not eligible for autologous stem cell transplantation are the intended participants.

Not a fit: Patients without TP53 aberrations, those who are eligible for standard curative options like ASCT, or individuals with medical contraindications to the study drugs are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could increase complete remissions and prolong disease control for patients with TP53‑mutant relapsed/refractory large B‑cell lymphoma who currently have poor outcomes.

How similar studies have performed: Combining bispecific antibodies such as glofitamab with checkpoint inhibitors and immunomodulatory drugs is a relatively new approach that has shown encouraging early‑phase activity in B‑cell lymphomas, but it is not yet proven specifically for TP53‑mutant disease.

Eligibility criteria

Inclusion Criteria:

* 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 Criteria:

* 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.

Where this trial is running

Nanjing, Jiangsu

• The First Affiliated Hospital with Nanjing Medical University — Nanjing, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Wei Xu Doctor

Conditions Large B-cell Lymphoma; TP53