Patients with immunotherapy-resistant non-muscle-invasive bladder cancer who received a novel combination treatment demonstrated improved 12-month response to treatment compared to standard treatment, according to a recent study published in Nature Medicine.
The combination of pembrolizumab chemotherapy and an oncolytic adenovirus therapy may serve as an alternative long-term treatment option for patients who are unable or unwilling to undergo high-risk bladder removal surgery, according to the authors.
“For our patients, this is a big step forward. BCG-unresponsive bladder cancer can be indolent, but death from bladder cancer is about 25 percent at five years. So, any victory that pushes a tumor into remission is a win,” said Joshua Meeks, ‘05 MD, ‘03 PhD, ‘06, ‘11 GME, the Edward M. Schaeffer, MD, PhD Professor of Urology and a co-author of the study.
In 2024, more than 83,000 cases of bladder cancer will be diagnosed in the U.S., according to estimates from the National Cancer Institute, and is more commonly diagnosed in men and individuals over the age of 55. Approximately 75 percent of cases will reach the non-muscle-invasive stage – in which cancer cells localize to the inner tissue lining of the bladder.
Standard treatment for non-muscle-invasive bladder cancer consists of surgical resection of the bladder followed by BCG immunotherapy. However, if the patient does not respond to BCG immunotherapy, the next step is bladder removal. The procedure is extremely high-risk and can result in long-term changes to a patient’s lifestyle, underscoring the need for alternative, non-invasive treatment options for patients.
In 2020, the FDA approved pembrolizumab chemotherapy for the treatment of non-muscle-invasive bladder cancer, but the 12-month response rate has remained just below 20 percent.
Cretostimogene grenadenorepvec, or CG0070, is an oncolytic adenovirus engineered to selectively replicate cancer cells with alterations in tumor suppressor pathways and support the immune system in targeting the bladder. The therapy, according to Meeks, has more cancer specificity and can rescue tumors that have evaded or exhausted the immune system.
In the current trial, more than 35 patients with non-muscle-invasive bladder cancer received a combination therapy of pembrolizumab and CG0070 weekly for six weeks. Patients who maintained complete response received three weekly maintenance infusions of CG0070 at three, six, nine, 12 and 18 months.
Overall, 83 percent of patients had a complete response to the treatment after three months and 57 percent had a complete response after 12 months.
“I think the major finding was the durability of the response at 12 months and very reasonable tolerability. Many of the patients were older with medical problems and who would not have done well with bladder removal. The hope is that this combination allows patients to keep their bladder and not need removal,” said Meeks, who is also an associate professor of Biochemistry and Molecular Genetics and a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.
Going forward, Meeks said his team aims to evaluate CG0070 without pembrolizumab in early-stage cancer and better characterize the mechanisms of treatment resistance that can inform the addition of other drugs to help decrease cancer recurrence.
This study was funded by CG Oncology in collaboration with Merck.