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

NCT07012980 | Not Yet Recruiting Phase 2

• 1 other identifier: SHZS-DLBCL004
• Study Type: interventional
• Target: 38
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Diffuse Large B-Cell Lymphoma

Keywords

glofitamab; polatuzumab vedotin; zanubrutinib; first-line; elderly; frail

Outcome Measures

Primary Outcomes (1)

• progression-free survival (PFS) rate

  defined as the time from the day of inclusion until disease progression (PD) or relapse after complete remission (CR) as per Lugano Classification of 2014, or death due to any cause, whichever occurs first.

  From the day of inclusion until disease progression (PD) or relapse after complete remission (CR) as per Lugano Classification of 2014, or death due to any cause, whichever occurs first, assessed up to 39 months.

Secondary Outcomes (3)

• CR rate

  up to 12 cycles, an avergae of 11 months

• DoR

  From documentation of CR/PR until relapse/progression or death due to any reason without documented relapse. Assessed up to 39 months.

• Incidence of treatment-related death rate

  defined as the number of treatment related deaths during therapy or up to 2 months after the end of study treatment, but before the start of further treatment, divided by the number of analyzable patients.

Study Arms (1)

Glofitamab, polatuzumab vedotin and zanubrutinib

EXPERIMENTAL

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.

Drug: Glofitamab; Drug: Polatuzumab Vedotin; Drug: Zanubrutinib

Interventions

Glofitamab 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.

Glofitamab, polatuzumab vedotin and zanubrutinib

Polatuzumab Vedotin 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).

Also known as: Polivy

Glofitamab, polatuzumab vedotin and zanubrutinib

Zanubrutinib DRUG

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

Glofitamab, polatuzumab vedotin and zanubrutinib

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Subjects will only be included in the study if they meet all the following criteria:
• Written informed consent.
• Aged 70 years old or above.
• ECOG performance status of 0-3.
• Histologically confirmed CD20 positive DLBCL.
• At least one measurable site of disease.
• Patient did not receive any prior lymphoma therapy.
• Patient has a life expectancy (in the opinion of the investigator) of at least 12 weeks.
• 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.
• 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).
• Patient has adequate renal function:

You may not qualify if:

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

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead
• Hoffmann-La Roche: collaborator
• BeiGene: collaborator

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

glofitamab; polatuzumab vedotin; zanubrutinib

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Peng Liu

  Fudan University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peng Liu

CONTACT

+86-021-64041990; liu.peng@zs-hospital.sh.cn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Physician

Study Record Dates

• First Submitted: May 24, 2025
• First Posted: June 10, 2025
• Study Start: June 1, 2025
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: June 10, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: starting 6 months after publication
• Access Criteria: IPD could be requested by contacting the corresponding author via email after publication.