Pirtobrutinib is an investigational, oral, highly-selective non-covalent Bruton’s tyrosine kinase (BTK) inhibitor. BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including chronic lymphocytic leukemia, mantle cell lymphoma, Waldenstrom’s macroglobulinemia, and marginal zone lymphoma.
Currently available BTK inhibitors irreversibly inhibit BTK and the long-term efficacy of these therapies can be limited by acquired resistance. Pirtobrutinib was designed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, preserve activity in the presence of the C481 acquired resistance mutations, and avoid off-target kinases that have complicated the development of both covalent and investigational non-covalent BTK inhibitors.
Pirtobrutinib is currently being studied in multiple clinical trials. Safety and efficacy have not been established for the uses being studied.
Pirtobrutinib is currently being evaluated in the following clinical trials:
BRUIN: a global, multi-center Phase 1/2 trial in patients with previously treated chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or non-Hodgkin’s lymphomas (NHL).
BRUIN CLL-321: a Phase 3 global, randomized, open-label study comparing pirtobrutinib to investigator's choice of either idelalisib plus rituximab or bendamustine plus rituximab in CLL/SLL patients who have been treated with at least a covalent BTK inhibitor.
BRUIN MCL-321: a Phase 3 open-label, randomized study of LOXO-305 versus investigator’s choice of BTK inhibitor in patients with previously treated BTK inhibitor-naïve mantle cell lymphoma.
BRUIN CLL-313: a Phase 3 open-label, randomized study of pirtobrutinib (LOXO-305) versus bendamustine plus rituximab in untreated patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
BRUIN CLL-322: a Phase 3 open-label, randomized study of fixed duration pirtobrutinib (LOXO-305) plus venetoclax and rituximab versus venetoclax and rituximab in previously treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- Pirtobrutinib, a Highly Selective, Non-Covalent (Reversible) BTK Inhibitor in Previously Treated Mantle Cell Lymphoma: Updated Results from the Phase 1/2 BRUIN Study
- Pirtobrutinib, A Highly Selective, Non-covalent (Reversible) BTK Inhibitor In Previously Treated CLL/SLL: Updated Results From The Phase 1/2 BRUIN Study
- Pirtobrutinib (LOXO-305), A Next Generation, Highly Selective, Non-Covalent BTK Inhibitor in Previously Treated Richter Transformation: Results from the Phase 1/2 BRUIN Study
- Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study
- LOXO-305, A Next Generation, Highly Selective, Non-Covalent BTK Inhibitor In Previously Treated CLL/SLL: Results From The Phase 1/2 BRUIN Study
- LOXO-305, a Next Generation, Highly Selective, NonCovalent BTK Inhibitor in Previously Treated Mantle Cell Lymphoma, Waldenstrom's Macroglobulinemia, and Other Non-Hodgkin Lymphomas: Results from the Phase 1/2 BRUIN Study
- In Vivo Pre-Clinical Evaluation of LOXO-305 Alone and in Combination with Venetoclax, R-CHOP or Obinutuzumab on Human Xenograft Lymphoma Tumor Models in Mice
- LOXO-305, a highly selective and non-covalent next generation BTK inhibitor, inhibits diverse BTK C481 substitution mutations
- Results from the First-in-Human, Proof-of-Concept Phase 1 BRUIN Trial in Pretreated B-Cell Malignancies for LOXO-305, a Next-Generation, Highly Selective, Non-Covalent BTK Inhibitor
- LOXO-305, A Next Generation Non-Covalent BTK Inhibitor, for Overcoming Acquired Resistance to Covalent BTK Inhibitors