Efficacy and Safety of Polatuzumab Vedotin in Combination With Zanubrutinib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone in Patients With Previously Untreated Diffuse Large B-Cell Lymphoma of the MCD/BN2/N1 Subtypes

NCT07608978 | Recruiting Phase 2

• 1 other identifier: 2026-SR-137
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, open-label, single-arm, single-center, Phase II clinical study designed to evaluate the efficacy and safety of Efficacy and Safety of Polatuzumab Vedotin in Combination With Zanubrutinib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone in Patients With Previously Untreated Diffuse Large B-Cell Lymphoma of the MCD/BN2/N1 Subtypes. After successful screening, enrolled patients will receive 6 treatment cycles (21 days per cycle). Disease response will be assessed by CT/PET-CT during treatment and after completion of induction. Patients who achieve CR/PR/SD will proceed to the maintenance phase; patients who do not achieve at least SD (i.e., fail to reach CR/PR/SD) during induction will discontinue the study. Patients with CR/PR/SD after induction will receive maintenance therapy with zanubrutinib plus tislelizumab until disease progression, unacceptable toxicity, or completion of 1 year of maintenance. Efficacy and safety assessments will be performed per protocol. Tumor response will be assessed by site investigators according to the 2014 Lugano criteria, including determination of response status, date of response, and date of progression/relapse.

Conditions

Diffuse Large B-Cell Lymphoma (DLBCL)

Outcome Measures

Primary Outcomes (1)

• 2-year Event-Free Survival rate（EFS）

  The duration from the start of treatment to the first occurrence of disease progression (per the 2014 Lugano Classification), relapse, initiation of new anti-lymphoma therapy, or death from any cause. EFS will be estimated using the Kaplan-Meier method, and between-arm comparisons will be conducted via the log-rank test. Participants who have not experienced any of these events by the end of follow-up will be censored at their last documented disease-evaluation date.

  Up to 2 years after start of treatment.

Secondary Outcomes (4)

• Complete response rate (CRR)

  Within 21 days after the completion of the 6th cycle of induction therapy (Each cycle is 21 days)

• Objective response rate (ORR)

  Within 21 days after the completion of the 6th cycle of induction therapy At the end of Cycle 1 (each cycle is 21 days)

• 2-Year Overall Survival (OS)

  Up to 2 years after start treatment

• Incidence of Treatment-Related Adverse Events (TRAE)

  From the first dose of study intervention to 30 days after the last dose of study intervention

Study Arms (1)

Pola+ZRCHP

EXPERIMENTAL

Previously untreated DLBCL patients harboring MCD/BN2/N1 subtypes were treated with Pola-ZRCHP (Polatuzumab Vedotin in Combination With Zanubrutinib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone，6 cycles, 21-day cycles), with Rituximab administered for 8 cycles. The regimen consisted of Polatuzumab vedotin (1.8 mg/kg IV, D1), Zanubrutinib (160 mg PO BID), and standard CHP (C 750 mg/m², H 50 mg/m² IV D1; P 100 mg PO D1-5). Following induction, patients achieving ≥Stable Disease (SD) per PET-CT entered the maintenance phase with Zanubrutinib (160 mg PO BID) and Tislelizumab (200 mg IV Q3W, up to 1 year), continuing until progression or unacceptable toxicity. Non-responders (\<SD) discontinued.

Drug: POLA-R-CHP+Zanubrutinib

Interventions

POLA-R-CHP+Zanubrutinib DRUG

Previously untreated DLBCL patients harboring MCD/BN2/N1 subtypes were treated with Pola-ZRCHP (Polatuzumab Vedotin in Combination With Zanubrutinib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone，6 cycles, 21-day cycles), with Rituximab administered for 8 cycles. The regimen consisted of Polatuzumab vedotin (1.8 mg/kg IV, D1), Zanubrutinib (160 mg PO BID), and standard CHP (C 750 mg/m², H 50 mg/m² IV D1; P 100 mg PO D1-5). Following induction, patients achieving ≥Stable Disease (SD) per PET-CT entered the maintenance phase with Zanubrutinib (160 mg PO BID) and Tislelizumab (200 mg IV Q3W, up to 1 year), continuing until progression or unacceptable toxicity. Non-responders (\<SD) discontinued.

Pola+ZRCHP

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years at the time of signing informed consent. Histologically confirmed Diffuse Large B-Cell Lymphoma (DLBCL) with MCD/BN2/N1 molecular subtypes defined by LymphGen classification.
• Previously untreated (treatment-naïve). International Prognostic Index (IPI) score of 2-5. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Life expectancy ≥6 months. At least one measurable lesion in two dimensions, defined as a maximum diameter \>1.5 cm by CT or MRI.
• Left Ventricular Ejection Fraction (LVEF) ≥50% as assessed by echocardiogram (ECHO).
• Adequate hematologic function (unless due to underlying disease, e.g., extensive bone marrow involvement, or splenomegaly secondary to splenic involvement deemed by the investigator to be caused by DLBCL; blood product transfusions are allowed), defined as follows:
• Hemoglobin ≥9.0 g/dL within 7 days prior to first treatment, without packed RBC transfusion.
• Absolute Neutrophil Count (ANC) ≥1.0 × 10⁹/L. Platelet count ≥75 × 10⁹/L. Female participants of childbearing potential: Must agree to abstain from heterosexual intercourse or use contraception, and agree not to donate ova.
• Male participants: Must agree to abstain from heterosexual intercourse or use contraception, and agree not to donate sperm.

You may not qualify if:

• Contraindication to any component of the Pola-ZRCHP regimen. Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding onychomycosis) at screening, or any major infection occurring within 4 weeks prior to the first dose of study treatment (as judged by the investigator).
• Suspected or latent tuberculosis (confirmed by positive IFNγ release assay). Currently pregnant or breastfeeding, or planning a pregnancy during the study period or within 12 months after the last dose.
• History of confirmed Progressive Multifocal Leukoencephalopathy (PML). Current or history of Central Nervous System (CNS) lymphoma. Evidence of significant, uncontrolled concomitant disease that may affect compliance with the protocol or interpretation of results.
• Severe or extensive cardiovascular disease, such as New York Heart Association (NYHA) Class III or IV, or objective assessment of Class C or D cardiac disease; myocardial infarction within the past 6 months; unstable arrhythmias; or unstable angina.
• Clinically significant liver disease, including active viral hepatitis or other hepatitis, current alcohol abuse, or cirrhosis.
• Any of the following abnormal laboratory values (unless these abnormalities are solely attributable to underlying lymphoma):
• INR or PT \>1.5 × Upper Limit of Normal (ULN) in the absence of therapeutic anticoagulation.
• PTT or aPTT \>1.5 × ULN in the absence of lupus anticoagulant. Serum AST and ALT ≥2.5 × ULN. Total bilirubin ≥1.5 × ULN. Estimated creatinine clearance \<40 mL/min (using the Cockcroft-Gault formula). Positive HBV DNA test result. Positive Hepatitis C test result (Hepatitis C virus \[HCV\] antibody serology). Note:Patients with positive HCV antibody are eligible only if the PCR test for HCV RNA is negative.
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that gives reasonable suspicion of a disease or condition that contraindicates the use of the investigational drug(s).

Sponsors & Collaborators

• The First Affiliated Hospital with Nanjing Medical University: lead

Study Sites (1)

Jiangsu Province Hospital

Nanjing, Jiangsu, 210000, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

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

• Wei Xu, PHD

  Hematological Department, Jiangsu Province Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jinhua Liang, MD

CONTACT

15952032421; 1151525490@qq.com

Wei Xu, PhD

CONTACT

xuwei10000@hotmail.com

Study Design

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

Model Details: a prospective, open-label, single-arm, single-center, Phase II clinical study designed to evaluate the efficacy and safety of Efficacy and Safety of Polatuzumab Vedotin in Combination With Zanubrutinib, Rituximab, Cyclophosphamide, Doxorubicin, and Prednisone in Patients With Previously Untreated Diffuse Large B-Cell Lymphoma of the MCD/BN2/N1 Subtypes After successful screening, enrolled patients will receive 6 treatment cycles (21 days per cycle). Disease response will be assessed by CT/PET-CT during treatment and after completion of induction. Patients who achieve CR/PR/SD will proceed to the maintenance phase; patients who do not achieve at least SD (i.e., fail to reach CR/PR/SD) during induction will discontinue the study. Patients with CR/PR/SD after induction will receive maintenance therapy with zanubrutinib plus tislelizumab until disease progression, unacceptable toxicity, or completion of 1 year of maintenance.

Study Record Dates

• First Submitted: May 20, 2026
• First Posted: May 27, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: May 27, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)