Glofitamab Plus Polatuzumab Vedotin and Zuberitamab in Patients With Newly Diagnosed Diffuse Large B-cell Lymphoma

NCT07231250 | Not Yet Recruiting Phase 2

• 1 other identifier: ML45750
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a multi-center, phase II, prospective study. The main purpose of study is to evaluate the efficacy and safety of Glofitamab plus Polatuzumab vedotin and Zuberitamab in patients with newly diagnosed diffuse large B-cell lymphoma.

Conditions

DLBCL - Diffuse Large B Cell Lymphoma; Chemo-free Therapy; Bispecific Antibody

Outcome Measures

Primary Outcomes (1)

• CR rate at C4D1

  CR rate, defined as the proportion of patients achieving complete remission at Cycle 4 Day 1.

  9 weeks

Secondary Outcomes (1)

• 2-yr Progression-free survival (PFS) rate

  2 years follow-up after EOT

Study Arms (1)

Trial group

EXPERIMENTAL

After receiving 3 cycles of Glofitamab plus Polatuzumab vedotin and Zuberitamab（Anti-CD20 Monoclonal Antibody）, patients were treated with Glofitamab plus Polatuzumab vedotin and Zuberitamab for 5 cycles if CR or Glofitamab plus Polatuzumab vedotin and Zuberitamab-CHP for 6 cycles if PR/SD based on iPET status.

Drug: Glofitamab; Polatuzumab vedotin; Zuberitamab; Cyclophosphamide; Doxorubicin; Prednisone

Interventions

Glofitamab; Polatuzumab vedotin; Zuberitamab; Cyclophosphamide; Doxorubicin; Prednisone DRUG

Step-up cycle (cycle 1) will comprise intravenous (i.v.) application of obinutuzumab 1,000 mg on D1, followed by i.v. application of polatuzumab vedotin 1.8 mg/kg on D2 and i.v. application of glofitamab in escalating doses of 2.5 mg on D8 and 10 mg on D15. Target dose phase (cycle 2-3) will comprise polatuzumab vedotin 1.8 mg/kg, i.v., glofitamab 30 mg i.v. and Zuberitamab 375mg/m2 i.v. on D1 and repeated Q3W. Adaptive treatment phase (cycle 4-9) will include two arms with dose cycle guided by PET/CT after C3: i.) If CR, it will comprise polatuzumab vedotin 1.8 mg/kg, i.v.(C4-6) on D1, glofitamab 30 mg i.v. (C4-8) on D2 and Zuberitamab 375mg/m2 i.v. (C4-8) on D1 and repeated Q3W. ii.) if PR or SD, it will comprise polatuzumab vedotin 1.8 mg/kg, i.v .(C4-6) on D1, glofitamab 30 mg i.v. (C4-8) on D8, Zuberitamab-CHP\[Zuberitamab 375mg/m2 i.v., cyclophosphamide i.v., doxorubicin i.v., and prednisone p.o. (C4-9)\] on D1 and repeated Q3W.

Trial group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The following criteria must be met to be eligible for the study:
• Written informed consent.
• Age ≥18 years at the time of signing the Informed Consent Form
• IPI score 2-5.
• ECOG performance status of 0-2.
• Histologically confirmed CD20-positive LBCL, including one of the following diagnoses by 2022 WHO classification of lymphoid neoplasms:
• DLBCL, not otherwise specified (NOS) including germinal B-cell type, activated B-cell type
• T-cell/histiocyte-rich large B-cell lymphoma
• Epstein-Barr virus-positive DLBCL, NOS
• Anaplastic lymphoma kinasepositive large B-cell lymphoma
• Kaposi's sarcomaassociated herpesvirus/human herpesvirus-8positive DLBCL
• DLBCL/HGBCL with MYC and BCL2 rearrangements
• HGBCL, NOS. (6) At least one measurable site of disease (\>1.5 cm long axis). (7) No previous treatment for lymphoma. (8) Life expectancy ≥6 months. (9) Left ventricular ejection fraction (LVEF) ≥50% on cardiac multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (ECHO) (10) Patient has adequate liver function:
• Total bilirubin ≤1.5 x ULN (≤3 x ULN in patients with Gilbert's syndrome).
• AST (aspartate aminotransferase) and ALT (alanine aminotransferase) ≤3 x ULN.

You may not qualify if:

• Patients who meet at least one of the following criteria are not eligible for trial participation:
• History of severe cardiac disease: New York Heart Association (NYHA) grade 3-4, congestive heart failure, myocardial infarction or cerebrovascular accident within the past 3 months, unstable arrhythmias, or unstable angina or history of multiple cardiovascular events) or significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm).
• Note: Congestive heart failure NYHA II patients can be included if they provide an LVEF \> 40%.
• Patient with current or history of CNS lymphoma.
• Patient with uncontrolled severe infection, whether bacterial (e.g., tuberculosis), viral (including, but not limited to severe pneumonia, COVID-19, Epstein-Barr virus \[EBV\], cytomegalovirus \[CMV\], hepatitis B, hepatitis C, and HIV\], fungal, mycobacterial, or other pathogens (excluding fungal infections of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics (for IV antibiotics this pertains to completion of last course of antibiotic treatment) within 4 weeks prior to study enrollment.
• Note: Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Patient with current \> Grade 1 peripheral neuropathy.
• Any other prior malignancy than non-melanoma skin cancer or stage 0 (in situ) cervical carcinoma, unless treated with curative intent, and without relapse since 2 years, or low grade prostate cancer, not in need of treatment
• Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study.
• Known hypersensitivity to hamster ovary (CHO) cell products or to any component of the Zuberitamab, polatuzumab vedotin, obinutuzumab, or glofitamab and/or to the contrast agents used in the study.

Sponsors & Collaborators

• Li Zhiming: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Dendritic Cell Sarcoma, Interdigitating

Interventions

glofitamab; polatuzumab vedotin; Cyclophosphamide; Doxorubicin; Prednisone

Condition Hierarchy (Ancestors)

Histiocytic Disorders, Malignant; Neoplasms by Histologic Type; Neoplasms; Histiocytosis; Lymphatic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienediols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds

Study Officials

• Zhiming Li, Professor

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhiming Li, Professor

CONTACT

+86 13719189172; lizhm@sysucc.org.cn

Peng Sun, Doctor

CONTACT

+86 18826437876; sunp@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: professor

Study Record Dates

• First Submitted: November 13, 2025
• First Posted: November 17, 2025
• Study Start: January 15, 2026
• Primary Completion (Estimated): September 15, 2026
• Study Completion (Estimated): September 15, 2028
• Last Updated: November 19, 2025

Record last verified: 2025-11

Locations

CN (1)