NCT06466122

Pirtobrutinib (LOXO-305) and Venetoclax for the Treatment of Patients With CLL or SLL Resistant to Covalent BTKi

Phase 2 Study of Combination Pirtobrutinib (LOXO-305) and Venetoclax in CLL Patients With Resistance to Covalent BTKi

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Kerry Rogers · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase II trial tests how well pirtobrutinib (LOXO-305) and venetoclax works in treating patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that remains despite treatment (resistant) with covalent bruton tyrosine kinase inhibitors (BTKi). Pirtobrutinib is in a class of medications called kinase inhibitors. It works by blocking the action of the a protein that signals cancer cells to multiply. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Giving pirtobrutinib and venetoclax may kill more cancer cells in patients with CLL or SLL that is resistant to covalent BTKi.

Detailed description

PRIMARY OBJECTIVE: I. Determine if combination pirtobrutinib and venetoclax can induce undetectable minimal residual disease (uMRD) in CLL patients with resistance to ibrutinib, acalabrutinib, or zanubrutinib. OUTLINE: Patients receive pirtobrutinib orally (PO) once daily (QD) on days 1-28 of each cycle and receive venetoclax PO QD on days 1-28 of cycles 2-20. Cycles repeat every 28 days for up to 20 cycles in the absence of disease progression or unacceptable toxicity. Patients who experience disease progression within 12 months of stopping combination treatment may receive pirtobrutinib PO QD in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, bone marrow aspiration and biopsy and computed tomography (CT) throughout the study. After completion of study treatment, patients are followed up every 6 months.

Conditions

• Chronic Lymphocytic Leukemia
• Small Lymphocytic Lymphoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo blood sample collection
PROCEDURE	Bone Marrow Aspiration	Undergo bone marrow aspiration and biopsy
PROCEDURE	Bone Marrow Biopsy	Undergo bone marrow aspiration and biopsy
PROCEDURE	Computed Tomography	Undergo CT
DRUG	Pirtobrutinib	Given PO
DRUG	Venetoclax	Given PO

Timeline

• Start date: 2024-11-07
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2024-06-20
• Last updated: 2026-02-19

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study