Evaluation of BGB-16673 Versus Pirtobrutinib in Relapsed/Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Patients

The primary objective of this study is to evaluate the efficacy of BGB-16673 compared to pirtobrutinib in patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma, as determined by progression-free survival through an independent review committee. Secondary objectives include the assessment of overall survival, additional efficacy endpoints, and the evaluation of safety. Furthermore, the study aims to monitor patient-reported outcomes, specifically regarding disease-related and treatment-specific symptoms and functional status.

This clinical trial involves 325 participants diagnosed with chronic lymphocytic leukemia or small lymphocytic lymphoma. The study population includes both male and female individuals within the specified age ranges. Participants must have a confirmed diagnosis according to the 2018 iwCLL criteria and require active treatment. Eligibility is restricted to patients whose disease has relapsed after or is refractory to at least one line of therapy involving a covalent Bruton tyrosine kinase inhibitor. For those with small lymphocytic lymphoma, the presence of measurable disease via computed tomography or magnetic resonance imaging is required. The primary objectives are:

• To evaluate the efficacy of BGB-16673 compared to pirtobrutinib.
• To assess progression-free survival as determined by an independent review committee.

This Phase 3, open-label, randomized study is designed to evaluate the safety and efficacy of BGB-16673 compared to pirtobrutinib in patients diagnosed with chronic lymphocytic leukemia or small lymphocytic lymphoma that is relapsed or refractory. The primary efficacy endpoint is progression-free survival, which is determined by an independent review committee. Secondary objectives include the assessment of overall survival, overall response rate, and the incidence of treatment-emergent adverse events. The study methodology involves the administration of oral film-coated tablets to the assigned groups. Participant involvement is estimated to continue through the projected end of the study period in November 2028.

The experimental medication consists of BGB-16673 administered as a film-coated tablet. The dosage is 200 mg, provided via oral use.

The comparator treatment is pirtobrutinib, marketed as Jaypirca. This medication is administered as film-coated tablets at a dose of 200 mg through oral use.

The primary efficacy endpoint is progression-free survival (PFS), defined as the interval from the date of randomization to the date of first disease progression or death. This parameter is determined by an independent review committee (IRC) utilizing modified 2018 International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria for patients with chronic lymphocytic leukemia and the Lugano classification for patients with small lymphocytic lymphoma.

Secondary efficacy assessments include:

• Overall survival (OS), defined as the time from randomization to death from any cause.
• PFS as determined by investigator assessment.
• Overall response rate, representing a partial response or better, assessed by both the IRC and investigator per the aforementioned disease-specific criteria.
• The rate of partial response with lymphocytosis or higher, determined by the IRC and investigator.
• Duration of response as evaluated by the IRC and investigator.
• Time to next anti-CLL/SLL treatment (TTNT).
• Patient-reported outcomes regarding global health status, role functioning, physical functioning, symptom burden, and physical condition or fatigue, measured via the EORTC quality of life questionnaire IL409.