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.
Parallel
Lisaftoclax
DrugLisaftoclax 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.
Pirtobrutinib
DrugPirtobrutinib 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.
Complete Response Rate at 6 Months in Cohort 1
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.
Overall Response Rate in Cohort 2
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.
Duration of Response
Progression-Free Survival
Overall Survival
Minimal Residual Disease Negativity Rate
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