RE:“Second mouse gets the cheese “December 05, 2023 - Results from a small phase 3 study presented at at the Society of Urologic Oncology conference conference last week suggest that cancer treatments, known as oncolytic viruses, bodes well for the dozens of other trials now underway. The data showed that an oncolytic virus developed by Irvine, California–based CG Oncology eliminated tumors in 64% of 66 patients with bladder cancer that didn’t respond to mainline treatment.
The phase 3 trial tested the virus in patients with a form of bladder cancer that hadn’t penetrated the muscular wall of the organ. If tumors like these grow unchecked, patients often need to have their bladders removed, but the virus may delay or prevent that outcome. Doctors assessed the participants every 3 months after the treatment began. In 76% of the patients, tumors were undetectable at one or more of these checkups. And in 74% of that group, the tumors did not return for at least 6 months. The study shows that “when you do everything well, you can get good clinical outcomes”.
“In the early days, we thought things would progress rapidly,” says virologist Grant McFadden of Arizona State University. The viruses—usually benign varieties such as the herpes simplex viruses and adenoviruses that are often modified to make them safer and more potent—can reproduce in tumor cells but not in healthy cells. Cancer cells are congenial for the viruses because they frequently shut down the first line of defense—known as the interferon response—against viral infections.
Doses of the viruses worked beautifully in animal studies, sometimes achieving 100% cure rates. But after more than 70 years of clinical trials around the world, only T-VEC, a modified herpes simplex virus type 1 (HSV1) that targets advanced melanoma, has performed well enough to receive the Food and Drug Administration’s go-ahead.hree other oncolytic viruses were OK’d outside the U.S., most recently a treatment for glioma brain tumors was approved in Japan in 2021.
Virologist Mary Hitt of the University of Alberta cites one reason for the clinical trial failures. At first, “everyone was afraid they wouldn’t be safe.” As a result, she says, many trials used weakened viruses that were too feeble to do much good. Another problem was that researchers didn’t understand how oncolytic viruses worked.
Now other candidate oncolytic viruses may soon get their chance.
An avenue to improve oncolytic viruses is pairing them with other immune therapies or with chemotherapy and radiation. Checkpoint inhibitors are obvious partners because they stymie tumors’ mechanisms for shutting down T cells. The company Oncolytics Biotech has performed two successful phase 2 trials of a tumor-attacking reovirus, combined with various types of chemotherapy and checkpoint inhibitors, in patients with breast cancer or pancreatic cancer. The company hopes to begin phase III trials of the virus for both cancer types as soon as 2024.
CG Oncology’s virus also performs well with pembrolizumab, a phase 2 study showed in 2022. A year after the treatment, tumors still hadn’t returned in 68% of bladder cancer patients. Pembrolizumab alone in this group usually eliminates tumors only in about 20% of patients, says urologic oncologist Roger Li of the Moffitt Cancer Center, who headed the trial and took part in the other CG Oncology study.
The many clinical trial failures frustrated researchers, but also paid off by convincing scientists and regulators that oncolytic viruses are safe, Immunologist Jianhua Yu of City of Hope says. Now, he and others are eager to show that they are potent as well. “They can have major impact,” McFadden says.
https://www.science.org/content/article/tumor-killing-viruses-score-rare-success-late-stage-trial