ROCKET-CLL Global Phase 3 Study: Rocbrutinib vs Pirtobrutinib in cBTKi-Pretreated R/R CLL/SLL

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.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* 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;
* Measurable disease;
* ECOG 0-2;
* Adequate marrow, hepatic, and renal function;
* TP53 mutation status confirmed by NGS;
* 17p deletion status confirmed by FISH;

Exclusion Criteria:

* Prior ncBTKi or BTK degraders;
* Richter's transformation;
* Confirmed prolymphocytic leukemia;
* Uncontrolled comorbidities or infections;
* Known CNS involvement by CLL/SLL;
* Prior malignancy requiring active treatment (except certain adequately treated cancers) per protocol;
* Pregnancy or breastfeeding;
* Concomitant medications or conditions prohibited by protocol (e.g., strong drug-drug interaction risk);