KT235 could help enable the body’s natural healing powers to keep both blood cancers and solid tumors in check
SCOTTSDALE, Ariz. — Nov. 21, 2023 — Cancer patients whose leukemia returns after initial treatments have few options and a poor prognosis, but a first-in-Arizona clinical trial opening at HonorHealth Research Institute is giving hope to those with this all-too-common blood cancer.
“This treatment is different from previous treatments as this does not involve cytotoxic chemotherapy … and the debilitating side effects associated with it,” said Rizwan Khawaja, M.D., a physician in the Cancer Research Division of HonorHealth Research Institute and the principal investigator of this clinical study.
Instead, under a clinical trial identified as NCT05775406, an experimental drug called KT235 targets and degrades a protein known as MDM2. Loss of MDM2 then allows a common gene called TP53 to produce a tumor suppressor protein known as P53, which can help prevent the cancer from growing out of control.
“In this study, we are hoping to harness the natural function of p53 to achieve disease control without the use of chemotherapy,” Dr. Khawaja said.
KT235 has been used by HonorHealth Research Institute since May 2023 to treat solid tumors as part of this clinical trial. In October, the trial was opened to patients with relapsed or refractory acute leukemia or high-grade myeloid malignancies after a pharmacologically active dose had been determined. It is intended to address a number of different cancers. The title of the clinical trial, sponsored by Kymera Therapeutics, is: Safety and Clinical Activity of KT253 in Adult Patients With High Grade Myeloid Malignancies, Acute Lymphocytic Leukemia, Lymphoma, Solid Tumors.
The P53 protein, known as the “guardian of the genome,” is commonly found throughout the body in the nucleus of cells, where it binds to DNA and helps regulate the cell cycle and cell division. When DNA is damaged by agents such as toxic chemicals, radiation or ultraviolet (UV) radiation from sunlight, P53 plays a critical role in determining whether the DNA can be repaired or if the damaged cell should self-destruct. By stopping cells with mutated or damaged DNA from dividing, P53 helps prevent the development of tumors.
P53 also is the most commonly mutated protein in the body. Once altered, P53 can no longer bind to the cell’s DNA, allowing DNA damage to accumulate in cells that then grow and divide to form a cancerous tumor.
Three primary blood cancers — Lymphoma, Myeloma and Leukemia — combine to kill more than 57,000 Americans annually.
This clinical study eventually could involve more than 60 patients who would be dosed every three weeks for as many as two years.
“Our next step will be to study this drug in larger number of patients with various types of blood and solid cancers,” Dr. Khawaja said. “Besides learning more about possible side effects and recommended doses, I hope that the trial will show cancer can be controlled by this novel mechanism.”