Dr. Taylor is studying compounds that destroy BTK molecules, to overcome drug resistancePatients with chronic lymphocytic leukemia (CLL) and related blood cancers often receive targeted treatments called BTK (Bruton's tyrosine kinase) inhibitors, which can shrink tumors and extend survival. However, some patients develop resistance to these drugs, limiting their treatment options.
A new study at Sylvester, led by researcher Justin Taylor, M.D., offers a promising solution with a next-generation BTK-targeting therapy that not only inactivates, but actually destroys, the BTK molecule, overcoming drug resistance.
Dr. Taylor and his team tested the new compound, NX-2127, in laboratory studies and a phase 1 clinical trial with patients whose tumors were resistant to previous treatments. The results were promising: The compound destroyed BTK molecules in patient cells and led to tumor shrinkage in 11 out of 14 CLL patients, including those who had developed resistance to approved BTK inhibitors.
NX-2127 is a BTK degrader, a new class of drug that binds to BTK and directs it to the cell's trash heap. Unlike current BTK inhibitors, which inhibit the enzyme, these degraders eliminate the target entirely. The therapy successfully overcomes various mutations in BTK that lead to resistance, a major breakthrough in treatment for CLL patients.
One notable case involved an elderly patient who had developed resistance to previous therapies. After receiving NX-2127, the patient's symptoms improved significantly, and he no longer required blood transfusions for anemia.
These encouraging findings could have broader implications, potentially treating other B-cell malignancies and autoimmune diseases. Dr. Taylor's team is now enrolling patients in a study testing an even more potent BTK degrader, NX-5948, offering hope for improved treatment options for those battling CLL and similar cancers.