Pirtobrutinib+Pola-R-CHP for Newly Diagnosed Non-GCB DLBCL

A Prospective, Multicenter Clinical Study of Pirtobrutinib Combined With Polatuzumab Vedotin, Rituximab, Cyclophosphamide, Doxorubicin and Prednisone (Pola-R-CHP) for Newly Diagnosed Non-GCB Diffuse Large B-Cell Lymphoma (DLBCL)

This is a single-arm, open-label, multicenter clinical study evaluating the efficacy and safety of pirtobrutinib combined with Pola-R-CHP in previously untreated Non-GCB DLBCL. PET/CT assessment will be performed after 3 cycles of combination therapy. Patients achieving CR/PR will continue treatment for another 3 cycles, while those with PD/SD will be discontinued from the study. Patients achieving CR/PR after 6 cycles of treatment will undergo follow-up with PET/CT or contrast-enhanced CT every 3 months during the first year and every 6 months thereafter, until disease progression, death, withdrawal of informed consent, or study completion, whichever occurs first.

Study Overview

• Status: Not yet recruiting
• Conditions: DLBCL - Diffuse Large B Cell Lymphoma; Pirtobrutinib
• Intervention / Treatment: Drug: Pirtobrutinib+Pola-R-CHP

• Study Type: Interventional
• Enrollment (Estimated): 48
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jianyong Li, PhD; Email: lijianyonglm@126.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China
      • Jiangsu Province Hospital The First Affiliated Hospital with Nanjing Medical University
      • Contact: Jianyong Li, PhD; Email: lijianyonglm@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed Non-GCB DLBCL (per 2016 WHO diagnostic criteria);
2. Whole-body PET/CT performed within 28 days prior to study enrollment demonstrating at least one measurable lesion (per 2014 Lugano criteria);
3. Age 18-65 years, with expected survival >3 months;
4. No prior anti-lymphoma treatment;
5. Signed written informed consent and ability to comply with protocol-required visits and procedures;
6. ECOG performance status 0-2;

7. Adequate organ and bone marrow function, defined as follows:

   • Hematology: Absolute neutrophil count (ANC) ≥1×10⁹/L, platelet count (PLT) ≥50×10⁹/L, hemoglobin (HGB) ≥8.0 g/dL; no granulocyte colony-stimulating factor, platelet transfusion, or red blood cell transfusion within 7 days prior to testing;
   • Hepatic function: Total bilirubin (TBIL) ≤1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN;
   • Renal function: Serum creatinine (Cr) ≤1.5×ULN or creatinine clearance (CCR) ≥50 mL/min;
   • Cardiac function: NYHA Class III or below; left ventricular ejection fraction ≥50% by echocardiography;
   • Coagulation: International normalized ratio (INR) ≤1.5×ULN, activated partial thromboplastin time (APTT) ≤ULN +10s, and prothrombin time (PT) ≤ULN +3s;
8. Women of childbearing potential or male subjects with partners of childbearing potential must use effective contraception throughout the treatment period and for 90 days after the last dose.

Exclusion Criteria:

1. Central nervous system involvement;
2. History of hypersensitivity to the study drug, drugs of the same class, or excipients;
3. Concurrent malignancy requiring treatment or intervention;
4. Major surgery within 4 weeks prior to treatment (excluding vascular access catheter placement or biopsy);
5. Presence of any life-threatening disease, medical condition, or organ system dysfunction that, in the investigator's opinion, may affect patient safety or compliance with study procedures;
6. Uncontrolled cardiac symptoms or disease, including: i. NYHA Class II or higher heart failure; ii. Unstable angina; iii. Myocardial infarction within 1 year; iv. Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention;
7. Active bleeding;
8. Active, uncontrolled systemic bacterial, viral, fungal, or parasitic infection (excluding onychomycosis), or other clinically significant active disease process that, in the investigator's opinion, renders the patient unsuitable for clinical trial participation;
9. Known history of human immunodeficiency virus (HIV) infection and/or acquired immunodeficiency syndrome;
10. Exclusion of patients with active chronic hepatitis B or active hepatitis C. Patients with positive hepatitis B surface antigen, hepatitis B core antibody, or hepatitis C virus antibody at screening must undergo further HBV-DNA and HCV-RNA testing. Patients with stable hepatitis B (HBV-DNA <2500 copies/mL or 500 IU/mL) on antiviral therapy and cured hepatitis C patients (below the limit of detection) may be enrolled;
11. Definitive history of neurological or psychiatric disorder, including epilepsy or dementia;
12. Pregnant or lactating women;
13. Receipt of other investigational agents within 1 month prior to first dose;
14. Any other factors that, in the investigator's opinion, may affect the evaluation of efficacy or safety in this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Pirtobrutinib+Pola-R-CHP for newly diagnosed non GCB DLBCL; This is a single-arm, open-label, multicenter clinical study evaluating the efficacy and safety of pirtobrutinib combined with Pola-R-CHP in previously untreated Non-GCB DLBCL. PET/CT assessment will be performed after 3 cycles of combination therapy. Patients achieving CR/PR will continue treatment for another 3 cycles, while those with PD/SD will be discontinued from the study. Patients achieving CR/PR after 6 cycles of treatment will undergo follow-up with PET/CT or contrast-enhanced CT every 3 months during the first year and every 6 months thereafter, until disease progression, death, withdrawal of informed consent, or study completion, whichever occurs first.

Drug: Pirtobrutinib+Pola-R-CHP; Pirtobrutinib 200 mg once daily Polatuzumab vedotin 1.8 mg/kg intravenously on Day 1 Rituximab 375 mg/m² on Day 1 Cyclophosphamide 750 mg/m² on Day 1 Doxorubicin 50 mg/m² on Day 1 Prednisone 100 mg on Days 1 to 5 Each cycle lasts 21 days. PET/CT evaluation is conducted after 3 treatment cycles. Subjects who attain CR or PR will receive an additional 3 cycles of therapy. Subjects with PD or SD will be withdrawn from the study. Subjects who do not achieve CR or PR upon completion of 6 cycles will be withdrawn from the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
2-year progression-free survival (PFS) rate	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective Response Rate (ORR) after 6 cycles of induction therapy	week 18，at the end of 6 cycles of induction therapy(each cycle is 21 days)
Complete Response Rate (CRR) after 6 cycles of induction therapy	week 18, at the end of 6 cycles of induction therapy(each cycle is 21 days)
Overall Survival(OS)	up to 4 years
Number of participants with treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0	up to 4 years

Collaborators and Investigators

• Sponsor: Changzhou No.2 People's Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2030

Study Registration Dates

• First Submitted: July 30, 2026
• First Submitted That Met QC Criteria: July 30, 2026
• First Posted (Actual): August 4, 2026

Study Record Updates

• Last Update Posted (Actual): August 6, 2026
• Last Update Submitted That Met QC Criteria: August 4, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Lymphatic Diseases; Histiocytic Disorders, Malignant; Histiocytosis; Hemic and Lymphatic Diseases; Dendritic Cell Sarcoma, Interdigitating
• Other Study ID Numbers: 2026CELH025-01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No