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.
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.
None
Single group
POLA-R-CHP+Zanubrutinib
DrugPreviously 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.
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.
Complete response rate (CRR)
The proportion of evaluable participants who achieve complete response (CR) following 6 cycles of induction therapy. CR is defined in accordance with the 2014 Lugano Classification for Lymphoma: this requires the complete disappearance of all measurable/evaluable lymphoma lesions, resolution of all disease-related clinical symptoms, and normalization of imaging findings (e.g., no residual measurable disease on CT/MRI, and no metabolically active disease on FDG-PET/CT). The analysis population is restricted to participants who complete at least 4 cycles of induction therapy and have available post-treatment efficacy assessment data.
Objective response rate (ORR)
The proportion of evaluable participants who achieve objective response (defined as complete response \[CR\] or partial response \[PR\]) following 6 cycles of induction therapy. Response assessment adheres to the 2014 Lugano Classification for Lymphoma: PR requires a ≥50% reduction in the sum of the longest diameters of measurable lesions, with no new lesions or progression of existing non-measurable disease. The analysis population includes participants who complete at least 4 induction cycles and have available post-treatment efficacy evaluation data.
2-Year Overall Survival (OS)
The duration from randomization to death from any cause. OS will be estimated using the Kaplan-Meier method, with between-arm comparisons performed using the log-rank test. Participants who remain alive at the 2-year follow-up endpoint will be censored at their last confirmed survival date.
Incidence of Treatment-Related Adverse Events (TRAE)
The proportion of participants experiencing any treatment-related adverse event, graded per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0. This includes the incidence of grade 3-4 TRAEs and serious adverse events (SAEs; defined as events that are life-threatening, require hospitalization, result in persistent disability, or are fatal).
Click on the lead sponsor to view all of their trials.
