Research report: UCLA researchers receive NIH grant to launch trial for immunotherapy-related diabetes

UCLA researchers have received a National Institutes of Health grant worth up to $7 million over five years to launch the first prospective human study of a treatment specifically aimed at immune checkpoint inhibitor-induced type 1 diabetes. The multicenter phase 1/2 trial will evaluate whether JAK inhibitors can protect insulin-producing pancreatic beta cells in people who develop diabetes after cancer immunotherapy. Researchers will also study the drugs’ safety, assess their effects on beta-cell function and determine whether they interfere with immunotherapy’s ability to control cancer.

The condition is estimated to affect 1% to 2% of patients treated with immune checkpoint inhibitors, drugs used in treating cancers including melanoma, lung cancer and kidney cancer. 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, producing immune-related adverse events that may affect the thyroid, liver, lungs, heart and pancreas.

When the response targets the pancreas, it can destroy insulin-producing cells and leave patients dependent on insulin for the rest of their lives. More than 5,000 patients have received checkpoint inhibitor therapies at UCLA alone, according to the researchers. The trial is based on laboratory and animal research led by 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.

In research published in JCI Insight, Lechner’s team identified a population of immune cells called T follicular helper cells as appearing to play an important role in checkpoint inhibitor-induced diabetes. These cells produce inflammatory signals, including interleukin-21 and interferon gamma, that contribute to the immune attack on pancreatic beta cells. The researchers subsequently 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, reversed the damage. Those findings provided the rationale for testing the approach in people, but the new study has not yet established whether the treatment will prevent diabetes or restore beta-cell function in patients. The clinical study, called JAK Inhibitor to STOP beta cell loss in checkpoint inhibitor Diabetes, or JAK STOP-DM (AMIB-ICIDM-01), will be conducted across the United States over five years.

It is expected to begin enrolling patients in early 2027. The trial will assess whether JAK inhibitors can protect beta cells in people who develop diabetes after receiving checkpoint inhibitor therapy, with safety and pancreatic beta-cell function among the outcomes under investigation. Another key question is whether blocking the implicated inflammatory pathways could reduce the effectiveness of immunotherapy against cancer.

Participants’ cancer control and the drugs’ biological and clinical effects will therefore be evaluated alongside safety. The project falls within UCLA’s broader efforts to understand and treat immune-related adverse events through the UCLA Autoimmunity Center of Excellence, a NIAID-funded program focused on developing new treatments for autoimmune diseases. The study will be co-led by Zoe Quandt of the University of California, San Francisco, with collaborators from UCLA.

Lechner said the trial was a direct extension of work aimed at understanding what drives autoimmune toxicities from cancer immunotherapy. The broader goal is to develop targeted treatments for serious side effects while preserving immunotherapy’s ability to fight cancer. The NIAID grant supports the trial under award number U01AI201291.

Because enrollment is expected to begin in early 2027, the study currently has no human efficacy results. Its phase 1/2 design will address unanswered questions in patients by measuring safety, beta-cell function and interference with cancer control, moving beyond the laboratory and animal findings that motivated the trial.

Subject of Research: A phase 1/2 trial of JAK inhibitors for immune checkpoint inhibitor-induced type 1 diabetes

Article Title: UCLA researchers receive NIH grant to launch trial for immunotherapy-related diabetes

Article References: UCLA researchers receive NIH grant to launch trial for immunotherapy-related diabetes. Original publication (Bibliographic details unavailable.)

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Keywords: immune checkpoint inhibitors, JAK inhibitors, type 1 diabetes, pancreatic beta cells, cancer immunotherapy, autoimmunity, clinical trial, NIH funding, UCLA, researchers, receive, grant