UCLA researchers have received a grant worth up to $7 million over five years from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), to launch a first-in-human clinical trial evaluating whether drugs already used to treat autoimmune diseases can prevent or reverse immune checkpoint inhibitor-induced type 1 diabetes, a rare but often permanent complication of cancer immunotherapy.
The multicenter phase 1/2 trial will be conducted across the U.S. over the next five years and will be the first prospective human study to test a treatment specifically aimed at the condition.
Immune checkpoint inhibitor-induced type 1 diabetes affects an estimated 1% to 2% of patients treated with immune checkpoint inhibitors, drugs that have become an important part of treatment for cancers including melanoma, lung cancer and kidney cancer. Although the complication is uncommon, it can destroy the insulin-producing cells in the pancreas and leave patients dependent on insulin for the rest of their lives.
“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 and a researcher at the UCLA Health Jonsson Comprehensive Cancer Center. “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 removing brakes on the immune system, allowing immune cells to recognize and attack cancer. The same heightened immune response can sometimes turn against healthy tissues, causing complications known as immune-related adverse events. These can affect organs including the thyroid, liver, lungs, heart and pancreas.
At UCLA alone, more than 5,000 patients have been treated with checkpoint inhibitor therapies, and many patients who develop immune-related adverse events experience treatment interruptions, hospitalizations and long-term organ damage.
Lechner's team has focused on what happens when the immune system attacks pancreatic beta cells, which produce insulin. In research published in JCI Insight, the researchers identified a population of immune cells called T follicular helper cells that appear to play an important role in the development of checkpoint inhibitor-induced diabetes. The cells produce inflammatory signals, including interleukin-21 and interferon gamma, that contribute to the immune attack on the pancreas.
The researchers found in preclinical studies that JAK inhibitors, a class of drugs already approved for several autoimmune and inflammatory conditions such as psoriasis and arthritis, can interfere with those signaling pathways. In some animal models, the treatment stopped the autoimmune attack on insulin-producing cells in the pancreas and, in some cases, even reversed the damage.
The new clinical trial, JAK Inhibitor to STOP beta cell loss in checkpoint inhibitor Diabetes or JAK STOP-DM (AMIB-ICIDM-01), will test whether that approach can work in people who develop diabetes after receiving checkpoint inhibitor therapy. Researchers will study the safety of the drugs and their effects on pancreatic beta-cell function, while also monitoring whether they interfere with the ability of immunotherapy to control 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. Our hope is that this approach will open the door to new ways of treating immune-related adverse events and help more patients safely benefit from cancer immunotherapy.”
The study is part of UCLA’s broader efforts to understand and treat immune-related adverse events through the UCLA Autoimmunity Center of Excellence, a NIAID-funded program (grant number U19AI181729) focused on developing new treatments for autoimmune diseases. The study will be co-led by Zoe Quandt, MD, from the University of California, San Francisco.
The project involves collaborators across UCLA, including Li-Jung Liang, Dr. Willy Hugo, Dr. Matt Freeby, Dr. Alexandra Drakaki and multiple research trainees.
The study is expected to begin enrolling patients in early 2027.
The clinical trial is supported by NIAID under grant number U01AI201291.
This content is solely the responsibility of UCLA and does not necessarily reflect the views of NIAID or NIH.
