Pirtobrutinib Maintenance After CAR-T Therapy in Relapsed or Refractory B-Cell Lymphoma

A Single-Arm, Open-Label, Multicenter Clinical Study to Evaluate the Efficacy and Safety of Pirtobrutinib as Maintenance Therapy for Relapsed or Refractory B-Cell Lymphoma After CAR-T Cell Therapy

This is a single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of pirtobrutinib as maintenance therapy in patients with relapsed or refractory B-cell lymphoma after commercial anti-CD19 CAR-T cell therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Relapsed or Refractory B-cell Lymphoma
• Intervention / Treatment: Drug: Pirtobrutinib; Biological: Second Infusion of Commercial Anti-CD19 CAR-T Cells

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center
      • Contact: Principal investigator; Phone Number: 0086-20-87342823; Email: caiqq@sysucc.org.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Able to understand and voluntarily sign the informed consent form.
• Age 18 years or older, male or female.
• Histologically confirmed large B-cell lymphoma, including diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, high-grade B-cell lymphoma, or transformed follicular lymphoma (tFL).
• Eastern Cooperative Oncology Group performance status of 0 to 2.
• Has received commercial anti-CD19 CAR-T cell therapy, with informed consent obtained before Day 28 after CAR-T cell infusion.
• Prior anti-lymphoma therapy-related adverse events, especially CAR-T-related adverse events, have stabilized and recovered to Grade 1 or lower, except for clinically insignificant toxicities.

Exclusion Criteria:

• History of other malignancies, except non-melanoma skin cancer without recurrence for more than 3 years, carcinoma in situ, such as cervical, bladder, or breast carcinoma, or follicular lymphoma.
• Prior autologous or allogeneic hematopoietic stem cell transplantation.
• Active or suspected uncontrolled fungal, bacterial, viral, or other infection requiring intravenous treatment. Patients with uncomplicated urinary tract infection or uncomplicated bacterial pharyngitis may be enrolled if responding to active treatment.
• History of immunodeficiency, including human immunodeficiency virus infection; positive treponema pallidum antibody; active hepatitis B virus infection; or active hepatitis C virus infection.
• Current or prior history of benign central nervous system disease, such as seizure, cerebrovascular ischemia or hemorrhage, dementia, cerebellar disease, or any central nervous system-related autoimmune disease.
• Lymphoma involvement of the atrium or ventricle.
• Autoimmune disease requiring systemic immunosuppressive or immunomodulatory therapy within 2 years.
• History of symptomatic deep vein thrombosis or pulmonary embolism within 6 months before enrollment.
• Any comorbidity that may affect or interfere with safety or efficacy assessment.

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 Maintenance After CAR-T Cell Therapy; Patients will receive pirtobrutinib 200 mg orally once daily starting on Day 30 after commercial anti-CD19 CAR-T cell infusion. Pirtobrutinib maintenance therapy will be continued for 6 months unless disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria occur. Patients who do not achieve complete response after 6 months of maintenance therapy, or who achieve complete response with detectable ctDNA, may receive a second infusion of commercial CAR-T cells at the investigator's discretion.

Drug: Pirtobrutinib; Pirtobrutinib will be administered orally at a dose of 200 mg once daily for 6 months, beginning on Day 30 after commercial anti-CD19 CAR-T cell infusion. Dose interruption, dose reduction, or treatment discontinuation will be performed according to protocol-specified toxicity management rules.; Biological: Second Infusion of Commercial Anti-CD19 CAR-T Cells; A second infusion of commercial anti-CD19 CAR-T cells may be administered after completion of 6 months of pirtobrutinib maintenance therapy in selected patients who do not achieve complete response, or who achieve complete response but remain ctDNA-positive, based on investigator assessment and protocol-defined criteria.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete response rate (CRR)	CRR is defined as the proportion of patients who achieve complete response according to the Lugano 2014 criteria at 6 months after initiation of pirtobrutinib maintenance therapy.	At 6 months after initiation of pirtobrutinib maintenance therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	OS is defined as the time from enrollment to death from any cause.	Up to 24 months
Best complete response rate (bCRR)	bCRR is defined as the proportion of patients whose best response is complete response according to the Lugano 2014 criteria.	Up to 24 months
Best objective response rate (bORR)	bORR is defined as the proportion of patients whose best response is complete response or partial response according to the Lugano 2014 criteria.	Up to 24 months
Objective response rate (ORR)	ORR is defined as the proportion of patients who achieve complete response or partial response according to the Lugano 2014 criteria at 6 months after initiation of pirtobrutinib maintenance therapy.	At 6 months after initiation of pirtobrutinib maintenance therapy
Duration of complete response (DoCR)	DoCR is defined as the time from the first documented complete response to disease progression or death from any cause, whichever occurs first.	Up to 24 months
Duration of response (DOR)	DOR is defined as the time from the first documented response to disease progression or death from any cause, whichever occurs first.	Up to 24 months
Progression-free survival (PFS)	PFS is defined as the time from enrollment to disease progression or death from any cause, whichever occurs first.	Up to 24 months
Incidence of adverse events (AEs) and serious adverse events (SAEs)	The incidence and severity of adverse events will be assessed and graded according to the National Cancer In Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.	Up to 30 days after the last dose of pirtobrutinib

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, B-Cell; pirtobrutinib
• Other Study ID Numbers: T2026-006

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