In collaboration with the UW Carbone Cancer Center, we are developing a new approach to the treatment of cancer that has spread beyond the primary tumor (metastatic cancer). This trial involves 3 ways to stimulate a patient’s own immune system to fight their cancer 1) “Immune checkpoint inhibition” (ICI), 2) “in situ vaccination” (ISV), and 3) low-dose radiopharmaceutical therapy (RPT).
ICI involves injections of a monoclonal antibody that targets the “immune checkpoints” (the “brakes”) of the immune system that cancer cells use to escape detection by cancer-killing immune cells. ICI therapy results in a lifting of the brakes and in some patients allows the immune system to recognize and actively kill cancer cells throughout the patient’s body. The ICI therapy used in this study is an IV drug called Gilvetmab that is USDA conditionally approved for use in dogs.
ISV involves a combination of standard doses of external beam radiation therapy (EBRT) that targets your dog’s primary cancer along with an injection directly into your dog’s primary cancer of an immune stimulant called PIC. The combination of EBRT and PIC has been shown in mouse tumors to turn the mouse’s own tumor into an anticancer vaccine resulting in cures in significant percentage of mice.
RPT involves giving a low dose of a radioactive molecule that is designed to target cancer cells specifically. This low dose does not kill cancer cells specifically, rather it changes the way the cancer cells are recognized by the patient’s immune system. We have shown that low-dose radiation, if delivered to all sites of cancer in a mouse, results in enhanced immune killing of the cancer cell.
This trial is seperated into 3 arms (Arm# 1, Arm# 2a, Arm# 2b). We will initially enroll patients to Arm #1. After completion of Arm# 1, patients will be randomized between Arm# 2a and Arm# 2b).
Clinical Protocol for Arm #1
Dogs with advanced (metastasized, spread) cancer may be eligible for this study. If your dog does enter the clinical trial, ICI therapy will start on Day 1. When your dog is to receive RPT, your dog would first receive an intravenous injection of a radioactive tracer, 86Y-NM600, which is an imaging agent (it is not therapeutic). PET/CT scans will be performed at 1-, 24-, and 48-hours post 86Y-NM600 injection. Your dog will be under general anesthesia for the PET/CT scans. Results of the PET/CT scans will allow us to determine the dose of RPT that will deliver the planned amount of radiation to all tumor sites. Because this is a radioactive substance, your dog would need to be hospitalized until it is determined that your dog is no longer radioactive (up to 6 days).
Clinical Protocol for Arm #2a and Arm# 2b
Dogs with advanced (metastasized, spread) cancer may be eligible for this study. If your dog does enter the clinical trial, ICI therapy will be started 2 weeks before receiving EBRT and intratumoral PIC. Only half of the dogs in this trial will receive RPT but all dogs will receive ICI, EBRT and intratumoral PIC- your dog will be randomized to either receive RPT or not in addition to the other treatments. If your dog is to receive RPT, your dog would first receive an intravenous injection of a radioactive tracer, 86Y-NM600, which is an imaging agent (it is not therapeutic). PET/CT scans will be performed at 1, 24, and 48 hours post 86Y-NM600 injection. Your dog will be under general anesthesia for the PET/CT scans. Results of the PET/CT scans will allow us to determine the dose of RPT that will deliver the planned amount of radiation to all tumor sites. Because this is a radioactive substance, your dog would need to be hospitalized until it is determined that your dog is no longer radioactive (up to 6 days).