LOXO-338 + pirtobrutinib

LOXO-338 + pirtobrutinib is an investigational, oral, small molecule drug combination under clinical evaluation for advanced hematologic malignancies. LOXO-338 is a selective small molecule inhibitor of B-cell lymphoma 2 (BCL2), designed to selectively target BCL2 over BCL-xL to avoid thrombocytopenia[2][3]. Pirtobrutinib (LOXO-305) is a highly selective, reversible, non-covalent inhibitor of Bruton's tyrosine kinase (BTK), developed to target both wild-type and mutant BTK. The combination seeks to leverage the complementary mechanisms of BCL2 inhibition–inducing apoptosis of malignant B-cells–and BTK inhibition–blocking B-cell receptor signaling to inhibit growth and survival of B-cell malignancies[1][3][7]. This combination is in phase 1 clinical trials primarily for relapsed/refractory B-cell malignancies, including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), non-Hodgkin lymphoma (NHL), mantle cell lymphoma, Waldenström macroglobulinemia, and multiple myeloma[1][3][5][7].