This is a Phase 3, randomized, open-label, multicenter study comparing rocbrutinib (LP-168) versus pirtobrutinib in adult participants with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received a covalent Bruton's tyrosine kinase inhibitor (cBTKi). Approximately 306 participants will be randomized 1:1 to receive rocbrutinib 200 mg orally once daily or pirtobrutinib 200 mg orally once daily, administered continuously in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, or other discontinuation criteria are met. Randomization will be stratified by presence of del(17p)/TP53 mutation (yes/no), reason for discontinuation of prior cBTKi therapy (toxicity vs disease progression), prior exposure to a BCL2 inhibitor (yes/no), and region (United States/China/rest of world). The primary endpoint is progression-free survival (PFS) assessed by an independent review committee (IRC) using iwCLL 2018 criteria for CLL and Lugano 2014 criteria for SLL. Key secondary objectives include overall survival, overall response rate, time-to-event outcomes, and safety/tolerability; exploratory objectives include health-related quality of life and biomarker assessments.
Age ≥18 years;
Histologically confirmed CLL/SLL iwCLL 2018;
Relapsed or refractory disease requiring treatment;
Previously treated with prior lines of therapy including a covalent BTK inhibitor;
Prior ncBTKi or BTK degraders;
Richter's transformation;
Confirmed prolymphocytic leukemia;
Uncontrolled comorbidities or infections;
Parallel
Rocbrutinib
DrugThe new generation, highly potent, ultra-selective BTK inhibitor with covalent and non-covalent dual binding mechanism, targeting both WT BTK and mutant BTK
Pirtobrutinib
DrugPirtobrutinib is a non-covalent BTK inhibitor.
PFS assessed by IRC
Progression-Free Survival assessed by independent review committee. PFS is defined as the time from the date of randomization to disease progression or death from any cause, whichever occurs first. Those who do not experience disease progression or death at the time of analysis are censored according to the last evaluation time point.
OS
Overall survival is defined as the time from the date of randomization to death from any cause. Those who did not die during the analysis were censored according to the last date the subject is known to be alive.
PFS assessed by INV
Progression free survival assessed by investigator
ORR
Overall response rate
DOR
Duration of response
Health related quality of Life
Health-related quality of life (HRQoL) will be assessed using validated patient-reported outcome (PRO) questionnaires to evaluate participants' functioning and symptoms over time. HRQoL endpoints will include change from baseline in overall health status and selected symptom and function domains. For the Global Health Status/QoL and functional scales, higher scores indicate better quality of life and functioning. For symptom scales/items, higher scores indicate greater symptom burden (worse symptoms).
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