Rocbrutinib versus pirtobrutinib for adults with relapsed or refractory CLL/SLL after a covalent BTK inhibitor

A Phase 3 Open-Label, Randomized, Multicenter Study of Rocbrutinib (LP-168) vs Pirtobrutinib in Covalent BTK Inhibitor (cBTKi) Pretreated Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL) Subjects

This compares rocbrutinib and pirtobrutinib to see which works better and is safer for adults whose CLL or SLL returned or didn't respond after a covalent BTK inhibitor.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 306 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Newave Pharmaceutical Inc (Industry-sponsored)
• Drugs / interventions: rocbrutinib, pirtobrutinib
• Locations: 3 sites (Las Vegas, Nevada and 2 other locations)
• Trial ID: NCT07342478 on ClinicalTrials.gov

What this trial studies

This is a randomized, open-label, global Phase 3 trial enrolling about 306 adults with relapsed or refractory CLL/SLL previously treated with a covalent BTK inhibitor. Participants are randomized 1:1 to receive oral rocbrutinib 200 mg once daily or oral pirtobrutinib 200 mg once daily in continuous 28-day cycles until progression, unacceptable toxicity, or other discontinuation criteria. Randomization is stratified by del(17p)/TP53 mutation status, reason for stopping prior cBTKi (toxicity vs progression), prior BCL2 inhibitor exposure, and geographic region. The primary endpoint is progression-free survival assessed by an independent review committee using iwCLL criteria, with additional safety and secondary efficacy measures collected.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed relapsed or refractory CLL or SLL who previously received a covalent BTK inhibitor, have measurable disease, ECOG 0–2, and adequate organ function are the intended participants.

Not a fit: Patients with prior non-covalent BTK inhibitor or BTK degrader exposure, Richter's transformation, CNS involvement, uncontrolled comorbidities or infections, or who are pregnant/breastfeeding are unlikely to benefit or are excluded.

Why it matters

Potential benefit: If successful, the comparison could identify a more effective or better-tolerated oral BTK inhibitor option for people with cBTKi-pretreated relapsed or refractory CLL/SLL and potentially extend progression-free survival.

How similar studies have performed: Pirtobrutinib has shown clinical activity and gained regulatory approval for cBTKi-pretreated CLL/SLL, while rocbrutinib is investigational and this head-to-head Phase 3 comparison is a novel direct test of the two agents.

Eligibility criteria

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);

Where this trial is running

Las Vegas, Nevada and 2 other locations

• Optum Medical Group (Rhodes) P.C. — Las Vegas, Nevada, United States (Recruiting)
• OSU Comprehensive Cancer Center — Columbus, Ohio, United States (Not_yet_recruiting)
• UPMC Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (Not_yet_recruiting)

Study contacts

• Study coordinator: Anna Y Chen, M.D., Ph.D.

Conditions CLL / SLL; CLL; CLL, Refractory; CLL, Relapsed; SLL; CLL Progression; Rocbrutinib; LP-168