This is the first full approval of the targeted drug therapy, which was developed and tested at the OSUCCC – James in collaboration with pharmaceutical partner Acerta Pharma. Marketed as Calquence®, acalabrutinib is a second-generation Bruton tyrosine kinase (BTK) inhibitor, a newer class of drugs shown to improve the survival of patients with mantle cell lymphoma in addition to CLL and SCL.
The drug works by permanently binding BTK, which is part of a chain of proteins that relays growth signals from the surface of the cancer cell to genes in the cell nucleus, enabling cancer cells to survive and grow. By blocking BTK, the drug halts the flow of these growth signals, and the cancer cells die.
Unlike the first generation BTK inhibitor (ibrutinib, marketed as IMBRUVICA®), preclinical and clinical data shows that acalabrutinib more selectively blocks the BTK pathway without disrupting other key molecular pathways important for preserving platelet and immune function, thereby preventing/minimizing certain side effects associated with cancer treatment.
The foundational basic-science research, initial phase I clinical trial and numerous sequential phase II and phase III clinical trials that led to this new FDA approval of acalabrutinib were performed by researchers at the OSUCCC – James led by John C. Byrd, MD.
This research included collaborative clinical trials with Ohio State’s College of Veterinary Medicine and the Comparative and Translational Oncology Program, a research collaboration that integrates nearly 40 scientific investigators from Ohio State’s colleges of Medicine, Pharmacy, Nursing and Veterinary Medicine, along with researchers from Nationwide Children’s Hospital, to investigate cancers that occur in both humans and animals. William Kisseberth, DVM, PhD, a professor in the College of Veterinary Medicine, directed the studies of acalabrutinib in dogs with lymphoma.
“Acalabrutinib is a potent and selective oral BTK inhibitor that has proven to be very effective for our patients affected by CLL and other blood cancers,” Byrd says.
Collaborator Jennifer Woyach, MD, of the Leukemia Research Program, presented data at the 61st annual meeting of the American Society of Hematology (ASH) on mechanisms of resistance that cause some patients to stop responding to acalabrutinib.