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