Mayo Clinic recently became the first institution to administer an investigational radioactive medicine to a patient with hepatocellular carcinoma (HCC), the most common type of liver cancer. The investigational medicine is a targeted radiopharmaceutical theranostic (RPT) that is designed to target a novel protein called glypican-3 (GPC3). The RPT was administered to the patient as part of a first-in-human clinical trial for the targeted therapy. This investigational RPT includes both a diagnostic imaging agent, intended to identify the cancer cells, and a therapeutic agent, intended to target and kill cancer cells.
GPC3 was identified as a potentially viable and promising target because it is produced at higher levels in HCC tissue than in a normal, healthy adult liver. It is also considered an oncofetal cell surface protein because GPC3 is normally only active during fetal development. In adults, the protein is turned off, but when cancer forms, it "reawakens" the protein to support rapid growth and evade the immune system. This means that GPC3 is found only on cancer cells, which makes it a strong potential target for treatment.
With this knowledge, Mayo Clinic researchers are participating in a first-in-human clinical trial investigating alpha-emitting RPTs, which use alpha particle radiation to precisely and powerfully diagnose, target, and potentially kill cancer cells. In this trial, the RPT includes an agent that binds to GPC3.
The phase 1/1b study is being conducted at all three academic Mayo Clinic sites in Rochester; Phoenix; and Jacksonville, Florida. The first person to receive the clinical trial procedure was at Mayo Clinic in Florida.
"Whole-body GPC3 targeted molecular imaging shows high localization to the tumor and minimal accumulation in normal tissues, indicating that the therapeutic radiation effects will be limited to sites of disease," says Ephraim Parent, M.D., Ph.D., a radiologist and division chair of Nuclear Medicine at Mayo Clinic in Florida. Dr. Parent is co-principal investigator on the trial.
Mayo Clinic in Florida researchers recently were the first in the U.S. to apply an investigational alpha-emitting radiopharmaceutical therapy in a treatment setting to a patient living with metastatic breast cancer. Mayo Clinic has now marked another remarkable first by delivering a different novel alpha-emitting investigational therapy to a patient with liver cancer, the second-leading cause of cancer-related deaths worldwide.
"At Mayo Clinic, we are committed to advancing innovative therapies that expand possibilities for those facing this devastating disease," says Lionel Kankeu Fonkoua, M.D., a medical oncologist at Mayo Clinic in Rochester and principal investigator of the trial. "Being able to offer access to this novel radiopharmaceutical approach reflects our dedication to pushing the boundaries of liver cancer care."
The drug for the study is being developed by RayzeBio Inc., a Bristol Myers Squibb Company, the sponsor of the active phase 1/1b clinical trial.
