eprenetapopt + acalabrutinib

Eprenetapopt + acalabrutinib is an investigational combination therapy under clinical evaluation for hematologic malignancies, particularly lymphoid and myeloid cancers. Eprenetapopt (also known as APR-246) is a small molecule that reactivates mutant tumor protein p53 to restore its tumor suppressor function, promoting apoptosis in cancer cells. Acalabrutinib is a highly selective Bruton tyrosine kinase (BTK) inhibitor that blocks BTK signaling required for the proliferation and survival of malignant B cells. The combination aims to target both p53-mutant pathways and B-cell receptor signaling in certain blood cancers. Eprenetapopt has received orphan drug and fast track designations for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), while acalabrutinib is approved as monotherapy or in combination with obinutuzumab for mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL). Clinical development of the eprenetapopt plus acalabrutinib regimen has been subject to FDA clinical holds due to safety concerns[2][3][4][8].