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

Summary

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.

Eligibility

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);

Conditions9

Interventions2

Locations4 sites

Find trials near these locations

Related trials

• A Phase 2 Trial of GlOfitamab anD pIrtobrutinib in Mantle Cell Lymphoma Patients With Prior BTK Inhibitor Exposure. — Australasian Leukaemia and Lymphoma Group
• Clonal Dynamics of Chronic Lymphocytic Leukaemia Treated With Pirtobrutinib After Previous Treatment With Zanubrutinib — Peter MacCallum Cancer Centre, Australia
• Pirtobrutinib, Lisaftoclax, and Rituximab in the Treatment of R/R DLBCL — The First Affiliated Hospital of Soochow University
• A Study of Pirtobrutinib (LY3527727) in Participants With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma — Eli Lilly and Company
• A Study Evaluating the Efficacy and Safety of Pirtobrutinib in Participants With Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma — Loxo Oncology, Inc.
• A Study to Evaluate the Safety and Efficacy of BGB-16673 Compared to Pirtobrutinib in Adults With Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma — BeOne Medicines
• A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) — Loxo Oncology, Inc.
• Glofitamab With Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma — University of California, San Francisco

Browse More Trials