UCLA researchers have received a federal grant worth up to $7 million over five years to launch a clinical trial examining whether drugs used to treat autoimmune diseases can prevent or reverse a rare form of diabetes caused by cancer immunotherapy, UCLA announced Tuesday.
The grant from the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, will fund a multicenter phase 1/2 trial expected to begin enrolling patients in early 2027.
Researchers said the trial will examine immune checkpoint inhibitor-induced type 1 diabetes, which affects an estimated 1% to 2% of patients treated with immune checkpoint inhibitors. The cancer treatments are used for melanoma, lung cancer, kidney cancer and other cancers.
The complication can destroy insulin-producing cells in the pancreas, leaving patients dependent on insulin for the rest of their lives, according to UCLA.
“Cancer immunotherapy has changed the lives of so many patients, but some of the immune-related side effects can be devastating,” said Dr. Melissa Lechner, an associate professor of medicine at the David Geffen School of Medicine at UCLA. “We hope this is just the first of many trials that will allow us to better prevent and treat immune-related adverse events while preserving the effectiveness of cancer immunotherapy.”
Immune checkpoint inhibitors work by allowing immune cells to recognize and attack cancer, but the heightened immune response can also attack healthy tissue. Such immune-related complications can affect the thyroid, liver, lungs, heart and pancreas, according to researchers.
More than 5,000 patients have been treated with checkpoint inhibitor therapies at UCLA, according to the university.
Previous research by Lechner’s team identified immune cells known as T follicular helper cells that appear to play a role in the development of checkpoint inhibitor-induced diabetes.
Researchers found in preclinical studies that JAK inhibitors, drugs already approved for some autoimmune and inflammatory conditions including psoriasis and arthritis, can interfere with inflammatory signaling pathways involved in the immune attack on the pancreas.
In some animal models, the treatment stopped the autoimmune attack on insulin-producing cells and in some cases reversed the damage, according to UCLA.
The new trial, called JAK STOP-DM, will test whether JAK inhibitors can protect pancreatic beta cells in people who develop diabetes after receiving checkpoint inhibitor therapy. Researchers will study the drugs’ safety and effects on beta-cell function while monitoring whether they interfere with immunotherapy’s ability to fight cancer.
“This trial is a direct extension of our work to understand what drives autoimmune toxicities from cancer immunotherapy,” Lechner said. “By identifying the pathways responsible for these complications, we can begin developing targeted treatments that protect patients from serious side effects without interfering with immunotherapy’s ability to fight cancer.”
The study will be co-led by Dr. Zoe Quandt of UC San Francisco and involves additional UCLA researchers.