A promising new trial is providing hope for patients with Bacillus Calmette-Guerin (BCG) unresponsive non-muscle invasive bladder cancer (NMIBC). Preliminary results from the CORE1 trial were presented at the 2022 American Association for Cancer Research Annual Meeting.

While bladder removal surgery is the gold standard treatment for BCG unresponsive NMIBC, the trial’s aim is to find an alternative option to help patients keep their bladders while preventing cancers from coming back. It combines immune checkpoint inhibitors with an oncolytic virus, CG0070, that is genetically engineered to attack cancer cells. The solution containing the virus is infused into the bladder to ignite an immune response, and that response is in turn amplified by the immunotherapy treatment that releases the natural brakes on the immune system.

Patients were given six weekly infusions of the virus inside their bladders, followed by three weekly maintenance therapies given every three months in the first year and every six months in the second year. Patients also received an immune checkpoint inhibitor, Pembrolizumab, every six weeks until year two.

“The oncolytic virus is thought to work through a two-pronged attack,” said Dr. Roger Li, a genitourinary surgeon at Moffitt Cancer Center and the CORE1 trial’s principal investigator. “First by targeting and destroying the cancer cells, and secondly, to stimulate an anti-tumor immune response.”

"The oncolytic virus is thought to work through a two-pronged attack, first by targeting and destroying the cancer cells, and secondly, to stimulate an anti-tumor immune response."

- Dr. Roger Li, Genitourinary Oncology Program

There were two key previous clinical trials that were performed using CG0070: a phase 1 V006 trial and a phase 2 BOND2 trial. These trials proved the treatment to be safe and effective, laying the groundwork for the CORE1 trial.

Li says clinical trials in the BCG unresponsive setting have traditionally been difficult due to patient heterogeneity and disagreements over trial endpoints.

“Typically, patients with this disease have their bladders surgically removed,” said Li. “Thus, interpretation of the efficacy data on drugs that can be used inside the bladder to keep the cancers from coming back can be difficult.”

Now with 35 patients enrolled in the CORE1 trial, researchers are starting to get a better idea of how they can effectively treat these patients and help to keep their bladders intact.

Moffitt's @UrogerliMD shares results of the CORE1 Phase 2, single arm study of CG0070 combined with pembrolizumab in patients with non-muscle invasive bladder cancer unresponsive to Bacillus Calmette-Guerin at an #AACR22 mini-symposium at 2:50 pm today. https://t.co/WqPZqR7nbN pic.twitter.com/BVIg1wo9T3

— Moffitt Cancer Center (@MoffittNews) April 12, 2022

“We’re seeing very promising preliminary results from this study,” said Li. “In the first 18 patients enrolled, all but two had a complete response that were seen at their three-month cystoscopy.”

According to Li, of the six patients to have reached the one-year mark, all had a complete response confirmed by a random bladder biopsy under cystoscopic guidance.

“There’s been a lot of work behind the scenes on developing the guidelines surrounding clinical trials in this disease space,” said Li. “Since then, pembrolizumab remains the only drug that has received FDA approval, demonstrating a three-month complete response rate of around 40%. Our results compare very favorably to that.”