Glofitamab, Polatuzumab Vedotin and Zanubrutinib in First-line Elderly DLBCL

NCT ID: NCT07012980

Last Updated: 2025-06-10

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 38 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-06-01
• Study Completion Date: 2026-07-31

Brief Summary

This study aims to assess the efficacy and safety of the chemotherapy-light combination of glofitamab, polatuzumab vedotin and zanubrutinib (GPZ) in elderly patients with previously untreated diffuse large B-cell lymphoma.

Detailed Description

This study is a prospective, single-center, interventional, phase 2 study. Each patient screend eligible for this study will receive a combination therapy of glofitamab, zanubrutinib and polatuzumab vedotin.

Conditions

Diffuse Large B-Cell Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Glofitamab, polatuzumab vedotin and zanubrutinib

Glofitamab will be administered i.v. on a step-up dosing schedule starting on Day 8 of Cycle 1 (2.5 mg), Day 15 of Cycle 1 (10 mg), followed by 30 mg on Day 1 of Cycles 2-6, with each cycle being 21 days.

A single dose of obinutuzumab 1000 mg will be administered intravenously on Day 1 of Cycle 1.

Polatuzumab vedotin (1.8 mg/kg) will be administered intravenously on Day 2 of Cycle 1 and on Day 1 of the subsequent Cycle 2-6 (each Q3W).

Zanubrutinib (160mg bid p.o.) will be administered for 7 days as pretreatment and from D1 to D21 through all 12 cycles Q3W.

Group Type: EXPERIMENTAL

Glofitamab

Intervention Type: DRUG

Glofitamab will be administered i.v. on a step-up dosing schedule starting on Day 8 of Cycle 1 (2.5 mg), Day 15 of Cycle 1 (10 mg), followed by 30 mg on Day 1 of Cycles 2-6, with each cycle being 21 days. A single dose of obinutuzumab 1000 mg will be administered intravenously on Day 1 of Cycle 1.

Polatuzumab Vedotin

Intervention Type: DRUG

Polatuzumab vedotin (1.8 mg/kg) will be administered intravenously on Day 2 of Cycle 1 and on Day 1 of the subsequent Cycle 2-6 (each Q3W).

Zanubrutinib

Intervention Type: DRUG

Zanubrutinib (160mg bid p.o.) will be administered for 7 days as pretreatment and from D1 to D21 through all 12 cycles Q3W.

Interventions

Glofitamab

Glofitamab will be administered i.v. on a step-up dosing schedule starting on Day 8 of Cycle 1 (2.5 mg), Day 15 of Cycle 1 (10 mg), followed by 30 mg on Day 1 of Cycles 2-6, with each cycle being 21 days. A single dose of obinutuzumab 1000 mg will be administered intravenously on Day 1 of Cycle 1.

Intervention Type: DRUG

Polatuzumab Vedotin

Polatuzumab vedotin (1.8 mg/kg) will be administered intravenously on Day 2 of Cycle 1 and on Day 1 of the subsequent Cycle 2-6 (each Q3W).

Intervention Type: DRUG

Zanubrutinib

Zanubrutinib (160mg bid p.o.) will be administered for 7 days as pretreatment and from D1 to D21 through all 12 cycles Q3W.

Intervention Type: DRUG

Other Intervention Names

Polivy

Eligibility Criteria

Inclusion Criteria

Subjects will only be included in the study if they meet all the following criteria:

1. Written informed consent.

2. Aged 70 years old or above.

3. ECOG performance status of 0-3.

4. Histologically confirmed CD20 positive DLBCL.

5. At least one measurable site of disease.

6. Patient did not receive any prior lymphoma therapy.

7. Patient has a life expectancy (in the opinion of the investigator) of at least 12 weeks.

8. 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. o Patients with documented liver involvement: AST and/or ALT ≤5 x ULN.

9. Patient as adequate hematological function, unless due to lymphoma:

• Hemoglobin ≥9.0 g/dL within 7 days before the first treatment.
• Absolute neutrophil count of ≥1.0 x 109 cells/L (1,000/μL).

10. Patient has adequate renal function:

• Creatinine ≤ 1.5 x ULN, or
• Creatinine clearance (CrCl) calculated by Cockcroft-Gault formula of ≥ 30 mL/min for patients in whom, in the Investigator's judgment, serum creatinine levels do not adequately reflect renal function.

Exclusion Criteria

Subjects will not be included in the study if any of the following criteria apply:

1. 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%.;

2. Patient with current or history of CNS lymphoma.

3. 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.

4. Patient with current > Grade 1 peripheral neuropathy.

5. 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

6. Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study.

7. Known hypersensitivity to Chinese hamster ovary (CHO) cell products or to any component of the zanubrutinib, polatuzumab vedotin, obinutuzumab, or glofitamab and/or to the contrast agents used in the study.

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• Minimum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

BeiGene

INDUSTRY

Sponsor Role: collaborator

Shanghai Zhongshan Hospital

OTHER

Sponsor Role: lead

Responsible Party

Peng Liu

Professor, Chief Physician

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Peng Liu

Role: PRINCIPAL_INVESTIGATOR

Fudan University

Central Contacts

Peng Liu

Role: CONTACT

liu.peng@zs-hospital.sh.cn

+86-021-64041990

Other Identifiers

SHZS-DLBCL004

Identifier Type: -

Identifier Source: org_study_id