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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
45
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.
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.
Henan Cancer Hospital
Zhengzhou, Henan, China
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.
Time frame: At 6 months after initiation of study treatment
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.
Time frame: From the first dose of study treatment until disease progression, assessed up to 36 months
Duration of Response
Time frame: 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
Overall Survival
Time frame: 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.
Number of Participants With Treatment-Emergent Adverse Events
Time frame: From the first dose of study treatment through 30 days after the last dose
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