A Real-World Study of Pirtobrutinib in cBTKi-Resistant/Intolerant Mature B-Cell Lymphoma

A Prospective, Multicenter, Real-World Study of Pirtobrutinib in Patients With Mature B-Cell Lymphoma Resistant or Intolerant to Covalent Bruton Tyrosine Kinase Inhibitors

This is a prospective, multicenter, real-world study to evaluate the efficacy and safety of pirtobrutinib in patients with mature B-cell lymphoma who are resistant or intolerant to prior covalent BTK inhibitors. The primary endpoint is overall response rate (ORR). Secondary endpoints include best overall response (BOR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. A total of 40 patients will be enrolled across 8 centers in China.

Study Overview

• Status: Not yet recruiting
• Conditions: Mature B-Cell Lymphoma
• Intervention / Treatment: Drug: Pirtobrutinib

Detailed Description

This prospective, multicenter, observational real-world study enrolls 40 patients with histologically confirmed mature B-cell lymphoma who have failed or are intolerant to at least one covalent BTK inhibitor. Patients receive pirtobrutinib 200 mg once daily until disease progression or unacceptable toxicity. Efficacy is assessed per Lugano 2014, iwCLL 2018, and IWWM-11 criteria. Safety is evaluated using CTCAE v5.0. The primary outcome is ORR. Secondary outcomes include BOR, DOR, PFS, OS, and safety profile.

• Study Type: Observational
• Enrollment (Estimated): 40

Contacts and Locations

• Study Contact: Name: Ou BAI, MD, PhD; Phone Number: +86-13039046656; Email: oubai16@163.com
• Study Contact Backup: Name: Jia Li, MD; Phone Number: +86 13844898514; Email: lijia0810@jlu.edu.cn

Study Locations

• China
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Bethune Hospital of Jilin University
      • Contact: Ou BAI, MD, PhD; Phone Number: +86-13039046656; Email: oubai16@163.com
      • Contact: Jia Li, MD; Phone Number: +86 13844898514; Email: lijia0810@jlu.edu.cn

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

This study enrolls 40 adult patients (≥18 years old) with histologically confirmed mature B-cell lymphoma who are resistant or intolerant to at least one prior covalent BTK inhibitor (cBTKi) therapy, across 8 clinical centers in China.

Description

Inclusion Criteria:

• Age ≥18 years;
• Histopathological confirmation of mature B-cell lymphoma, primarily including CLL/SLL, MCL, FL, MZL, WM/LPL, etc.;
• Disease progression and/or intolerance after prior treatment with ≥1 cBTKi (including ibrutinib, ibrutinib, zanubrutinib, or acitinib);
• ECOG PS 0-2;
• Adequate liver and kidney function: the following criteria must be met simultaneously: 1) AST and ALT ≤ 3×ULN; 2) Total bilirubin ≤ 1.5×ULN; 3) Creatinine clearance rate ≥ 30 mL/min;
• Participants must be voluntary and capable of completing the study procedures and follow-up examinations;
• Informed consent must be obtained voluntarily prior to screening.

Exclusion Criteria:

• Patients with known allergic reactions to any component or excipient of piteutinib;
• Patients concurrently participating in other clinical studies;
• A history of clinically significant, uncontrolled cardiac,
• Cardiovascular disease, or myocardial infarction within 6 months prior to planned initiation of piteutinib therapy;
• Uncontrolled systemic bacterial, viral, fungal, or parasitic infections; current use of potent CYP3A4 inhibitors or inducers and/or potent P-gp inhibitors;
• Positive human immunodeficiency virus (HIV) testing;
• Active hepatitis B or C: 1) Patients with positive hepatitis B virus (HBV) DNA testing and controlled disease status may be enrolled with investigator approval. For HBV DNA-positive patients, concurrent antiviral therapy is required. 2) Patients with prior hepatitis C virus (HCV) infection history who have completed antiviral therapy with viral loads below the quantitative limit may be enrolled;
• Based on the investigator's assessment, participants may be unable to complete all study protocol requirements, including follow-up visits, and/or adhere to all study procedures;
• A history of other clinically significant diseases or comorbidities; and any safety risks or potential interference with study completion as evaluated by investigators.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pirtobrutinib Treatment Cohort; Patients with cBTKi-resistant/intolerant mature B-cell lymphoma receiving pirtobrutinib 200 mg once daily in real-world clinical practice.Receive pitobrutinib as monotherapy or in combination, with a recommended dose of 200 mg once daily until disease progression or unacceptable toxicity occurs.	Drug: Pirtobrutinib; Pirtobrutinib 200 mg administered orally once daily, in accordance with standard clinical practice, until disease progression, unacceptable toxicity, or study completion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Overall Response Rate	24months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS	Overall Survival	24 months
PFS	Progression-Free Survival	24 months
BOR	Best Overall Response	24 months
DOR	Duration of Response	24 months
Number of participants with treatment-related adverse events (TRAEs) as assessed by CTCAE v5.0	Incidence, severity (graded per CTCAE v5.0), and causality of all adverse events (AEs), serious adverse events (SAEs), and treatment-related adverse events (TRAEs) from the first dose of pirtobrutinib to 30 days after the last dose.	24 months

Collaborators and Investigators

• Sponsor: Ou Bai, MD/PHD

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Pirtobrutinib; Covalent BTK inhibitor; Mature B-cell lymphoma
• Additional Relevant MeSH Terms: pirtobrutinib
• Other Study ID Numbers: 25K492-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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