Lisaftoclax Plus Pirtobrutinib in Relapsed or Refractory Mantle Cell Lymphoma After BTK-Targeted Therapy

June 29, 2026 updated by: KeshuZhou, Henan Cancer Hospital

A Prospective Phase 2 Study of Lisaftoclax Plus Pirtobrutinib in Patients With Relapsed or Refractory Mantle Cell Lymphoma After Failure of BTK-Targeted Therapy

This prospective, open-label, phase 2 study will evaluate the efficacy and safety of lisaftoclax in combination with pirtobrutinib in adults with relapsed or refractory mantle cell lymphoma following failure of prior BTK-targeted therapy.

The study includes two cohorts. Cohort 1 will enroll participants who experienced stable disease, disease progression, or intolerance following treatment with a covalent BTK inhibitor. Cohort 2 is an exploratory cohort enrolling participants who experienced stable disease, disease progression, or intolerance following treatment with a non-covalent BTK inhibitor other than pirtobrutinib or a BTK degrader.

Participants will receive oral pirtobrutinib 200 mg once daily in combination with oral lisaftoclax. Lisaftoclax will be administered using a dose ramp-up schedule, followed by a target dose of 600 mg once daily. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

45

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Henan
      • Zhengzhou, Henan, China
        • Henan Cancer Hospital
        • Principal Investigator:
          • Keshu Zhou
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Participants must meet all of the following criteria:

    1. Age 18 years or older.
    2. Histologically and immunophenotypically confirmed mantle cell lymphoma.
    3. At least one measurable lesion.
    4. Received at least one prior systemic treatment regimen that included a BTK-targeted therapy, including a covalent BTK inhibitor, non-covalent BTK inhibitor, or BTK degrader, and had stable disease, disease progression, or intolerance during or after the most recent BTK-targeted therapy.
    5. Eastern Cooperative Oncology Group performance status of 0 to 2.

    6. Adequate hepatic, renal, and bone marrow function, defined as all of the following:

      * Aspartate aminotransferase and alanine aminotransferase ≤3 × upper limit of normal;

      • Total bilirubin ≤1.5 × upper limit of normal;
      • Creatinine clearance ≥30 mL/min;
      • Absolute neutrophil count ≥0.5 × 10^9/L;
      • Platelet count ≥30 × 10^9/L. Supportive treatment is permitted.
    7. Participants of reproductive potential must agree to use effective contraception during study treatment and for 3 months after the last dose of study treatment.
    8. Willing and able to comply with study procedures and follow-up assessments.
    9. Able to understand and voluntarily sign the informed consent form before screening.

Exclusion Criteria:

  • 1. Known hypersensitivity to pirtobrutinib, lisaftoclax, or any component or excipient of either study drug.

    2. Concurrent participation in another clinical study. 3. Prior treatment with any BCL-2 inhibitor. 4. Active central nervous system involvement, including parenchymal or leptomeningeal disease.

    5. Clinically significant uncontrolled cardiac or cardiovascular disease, or a history of myocardial infarction within 6 months before the planned initiation of pirtobrutinib.

    6. Uncontrolled active severe systemic bacterial, viral, fungal, or parasitic infection.

    7. Current treatment with strong CYP3A4 inhibitors or inducers and/or strong P-glycoprotein inhibitors.

    8. Positive human immunodeficiency virus test. 9. Active hepatitis B or hepatitis C infection, except:

    • Participants with detectable hepatitis B virus DNA whose disease is controlled may be enrolled at the investigator's discretion, provided that concurrent antiviral therapy is administered;

    • Participants with a history of hepatitis C virus infection who have completed antiviral treatment and have a viral load below the lower limit of quantification may be enrolled.

      10. Pregnant or breastfeeding women. 11. Unable to complete protocol-required study visits or procedures, including follow-up visits, or unable to comply with study requirements.

      12. Any other clinically significant current or prior medical condition that, in the investigator's judgment, may pose a risk to participant safety or interfere with study assessments, procedures, or completion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort 1: Prior Covalent BTK Inhibitor Therapy
Participants with relapsed or refractory mantle cell lymphoma who experienced stable disease, disease progression, or intolerance following prior treatment with at least one covalent BTK inhibitor will receive lisaftoclax in combination with pirtobrutinib.
Drug: Lisaftoclax
Lisaftoclax will be administered orally once daily. During Cycle 1, participants will undergo dose ramp-up with 20 mg on Day 1, 50 mg on Day 2, 100 mg on Day 3, 200 mg on Day 4, and 400 mg on Day 5. The target dose of 600 mg once daily will begin on Day 6 and continue thereafter. Each treatment cycle is 28 days. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined reason for discontinuation.
Drug: Pirtobrutinib
Pirtobrutinib will be administered orally at a dose of 200 mg once daily beginning on Day 1 of Cycle 1. Each treatment cycle is 28 days. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined reason for discontinuation.
Experimental: Cohort 2: Prior Non-Covalent BTK Inhibitor or BTK Degrader Therapy
Participants with relapsed or refractory mantle cell lymphoma who experienced stable disease, disease progression, or intolerance following prior treatment with a non-covalent BTK inhibitor other than pirtobrutinib or a BTK degrader will receive lisaftoclax in combination with pirtobrutinib.
Drug: Lisaftoclax
Lisaftoclax will be administered orally once daily. During Cycle 1, participants will undergo dose ramp-up with 20 mg on Day 1, 50 mg on Day 2, 100 mg on Day 3, 200 mg on Day 4, and 400 mg on Day 5. The target dose of 600 mg once daily will begin on Day 6 and continue thereafter. Each treatment cycle is 28 days. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined reason for discontinuation.
Drug: Pirtobrutinib
Pirtobrutinib will be administered orally at a dose of 200 mg once daily beginning on Day 1 of Cycle 1. Each treatment cycle is 28 days. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined reason for discontinuation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response Rate at 6 Months in Cohort 1
Time Frame: At 6 months after initiation of study treatment
The proportion of participants in Cohort 1 who achieve a complete response at 6 months after initiation of study treatment, as assessed by the investigator according to the Lugano 2014 response criteria.
At 6 months after initiation of study treatment
Overall Response Rate in Cohort 2
Time Frame: From the first dose of study treatment until disease progression, assessed up to 36 months
The proportion of participants in Cohort 2 who achieve a best overall response of complete response or partial response, as assessed by the investigator according to the Lugano 2014 response criteria.
From the first dose of study treatment until disease progression, assessed up to 36 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Duration of Response
Time Frame: From the first documented response until disease progression or death, whichever came first, assessed up to 36 months
From the first documented response until disease progression or death, whichever came first, assessed up to 36 months
Progression-Free Survival
Time Frame: From the first dose of study treatment until disease progression or death, whichever came first, assessed up to 36 months
From the first dose of study treatment until disease progression or death, whichever came first, assessed up to 36 months
Overall Survival
Time Frame: From the first dose of study treatment until death from any cause, assessed up to 36 months
From the first dose of study treatment until death from any cause, assessed up to 36 months
Minimal Residual Disease Negativity Rate
Time Frame: At baseline, assessed up to 4 weeks. Interim response assessment, from the first dose of study treatment till 3 cycles. End of induction treatment, from the first dose of study treatment till 3 cycles. Following period, every 6 months during follow-up.
At baseline, assessed up to 4 weeks. Interim response assessment, from the first dose of study treatment till 3 cycles. End of induction treatment, from the first dose of study treatment till 3 cycles. Following period, every 6 months during follow-up.
Number of Participants With Treatment-Emergent Adverse Events
Time Frame: From the first dose of study treatment through 30 days after the last dose
From the first dose of study treatment through 30 days after the last dose

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Henan Cancer Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

June 30, 2026

Primary Completion (Estimated)

October 30, 2028

Study Completion (Estimated)

April 30, 2029

Study Registration Dates

First Submitted

June 17, 2026

First Submitted That Met QC Criteria

June 29, 2026

First Posted (Actual)

July 6, 2026

Study Record Updates

Last Update Posted (Actual)

July 6, 2026

Last Update Submitted That Met QC Criteria

June 29, 2026

Last Verified

June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2026-204

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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