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

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are indolent B-cell malignancies characterized by accumulation of mature but dysfunctional lymphocytes. Covalent Bruton's tyrosine kinase inhibitors (cBTKis) have substantially improved outcomes for patients with CLL/SLL; however, disease progression on cBTKi therapy or intolerance leading to treatment discontinuation remains an important clinical challenge. Patients who discontinue cBTKi therapy due to progression have limited therapeutic options and may experience poor outcomes. Therefore, effective and well-tolerated therapies are needed for participants with relapsed or refractory (R/R) CLL/SLL who have previously received a covalent BTK inhibitor.

Rocbrutinib (LP-168) is a selective next-generation inhibitor of BTK, that can irreversibly inhibit WT BTK, and reversibly inhibit C481 mutated BTK, with activity against known resistance mutations for non-covalent BTKi, under investigation for the treatment of CLL/SLL. Pirtobrutinib is an oral BTK inhibitor with regulatory approval for adults with R/R CLL/SLL who have previously received a covalent BTK inhibitor (cBTKi). This Phase 3 study is designed to compare the efficacy and safety of rocbrutinib versus pirtobrutinib in adult participants with cBTKi-pretreated R/R CLL/SLL.

This is a Phase 3, randomized, open-label, multicenter study conducted at approximately 100 sites globally. Approximately 306 participants will be randomized in a 1:1 ratio to receive rocbrutinib (LP-168) or pirtobrutinib. Eligible participants are adults with confirmed R/R CLL or SLL who require therapy and have received prior treatment with a cBTKi. Participants may have received additional prior systemic therapies, including prior exposure to a BCL2 inhibitor. Key exclusion criteria include central nervous system involvement by CLL/SLL and clinically significant cardiovascular conditions, including uncontrolled arrhythmias and clinically relevant QTc prolongation.

Participants randomized to the investigational arm will receive rocbrutinib 200 mg orally once daily. Participants randomized to the active comparator arm will receive pirtobrutinib 200 mg orally once daily. Study treatments will be administered continuously in 28-day cycles until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria. Crossover between treatment arms is not permitted.

Randomization will be stratified based on prognostic and treatment-history factors, including: (1) del(17p) and/or TP53 mutation status, (2) reason for discontinuation of prior cBTKi therapy, (3) prior exposure to a BCL2 inhibitor, and (4) geographic region.