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

Inclusion criteria

• Participants must meet all of the following criteria:

• Age 18 years or older.
• Histologically and immunophenotypically confirmed mantle cell lymphoma.
• At least one measurable lesion.
• 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.
• Eastern Cooperative Oncology Group performance status of 0 to 2.
• 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.
• Participants of reproductive potential must agree to use effective contraception during study treatment and for 3 months after the last dose of study treatment.
• Willing and able to comply with study procedures and follow-up assessments.
• 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.

• 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.

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

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

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

• 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.

• 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.

• 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.