Background 

Bacillus Calmette-Guérin (BCG) is one of the main treatments for people with non-muscle-invasive bladder cancer (NMIBC). This therapy helps the immune system attack cancer cells and can keep the disease from coming back in many patients. However, for a large number of people, the cancer eventually returns even after BCG treatment. When this happens, doctors often recommend surgery to remove the bladder, which can be life-changing and difficult for patients. Scientists still don’t fully understand why BCG stops working in some cases. 

What the Study Proposes to Address 

Researchers recently discovered that after BCG treatment, some bladder tumors begin to produce proteins that help them hide from the immune system. These proteins—called NKG2A and PD-1 on immune cells, and HLA-E and PD-L1 on cancer cells—act like shields that stop the body from recognizing and killing the cancer. The team believes that blocking these proteins could help the immune system fight back. To test this, the study will launch a Phase 2 clinical trial using two drugs, durvalumab and monalizumab, that target these specific proteins. The researchers will also study whether measuring HLA-E and NKG2A in tumor samples before treatment can help identify which patients are most likely to benefit from this new therapy. 

Why This Research is Important 

This study could lead to a major step forward in treating bladder cancer that no longer responds to BCG. By targeting the proteins that allow cancer to hide, doctors may be able to restore the immune system’s ability to fight the disease and reduce the need for bladder removal surgery. The trial was developed with help from bladder cancer survivors and advocates, ensuring that the research reflects patient needs and priorities. If successful, this project could offer new, less invasive treatment options and improve survival and quality of life for many people with high-risk bladder cancer. 

None Reported as of August 2025

None Reported as of August 2025

Matthew Galsky, MD; Icahn School of Medicine at Mount Sinai
John Sfakianos, MD; Icahn School of Medicine at Mount Sinai