City of Hope, a world-renowned research and treatment organization for cancer, diabetes, and other life-threatening diseases, recently announced the initiation of a first-in-human clinical trial evaluating the use of an anti-cancer oncolytic virus drug for the treatment of patients with metastatic triple-negative breast cancer (TNBC).
The CF33-hNIS-antiPDL1 therapy, developed by City of Hope, is genetically modified from a natural virus (chimeric oncolytic orthopoxvirus) and designed to infect, replicate, and kill cancer cells while protecting healthy cells. Imugene Ltd., a company that develops immunotherapies to activate the immune system of cancer patients to treat and eradicate tumors, has been granted a patent covering CF33-hNIS-antiPDL1.
“The purpose of this study is to determine the safety and the optimal biological dose that may induce an immune response in triple-negative breast cancer,” said Yuan Yuan, M.D., principal investigator of the Phase I clinical trial and associate professor in the Department of Medical Oncology & Therapeutics Research at City of Hope. “Currently approved therapies are not curative for this aggressive form of breast cancer that is often resistant to chemotherapy. Clinical trials like this one are seeking lasting efficacy and better quality of life for patients.”
Researchers are trying to determine the appropriate dose of CF33-hNIS-antiPDL1 and to determine whether this therapy is safe and likely to be effective for patients with TNBC that is advanced or has spread to other parts of the body. The test will be conducted in patients whose cancer has progressed with standard-of-care chemotherapy.
TNBC affects approximately 15-20% of all breast cancer patients. This is an extremely challenging disease to treat—most FDA-approved therapies can extend survival by a median of two years. Despite recent FDA approval of targeted therapies targeting BRCA gene mutations (i.e., the immune checkpoint inhibitor pembrolizumab and Trop-2 antibody drug couples), most patients continue to have cancer progression after the first two lines of therapy. Despite the availability of prior therapeutic options, the needs of patients with TNBC have not been met.
Researchers have observed cancer-killing effects of CF33 in the preclinical setting against the following cancer cell types: pancreatic, gastric, lung, ovarian, and colon. Published preclinical data suggest that the CF33 virus has an enhancing effect on immune checkpoint inhibitors, which helps improve the immune system’s ability to do its job.
“This is an exciting time in immuno-oncology. Preclinical studies have shown that this oncolytic virus can directly kill cancer and stimulate the immune system to further eradicate cancer. This trial is an important step forward.” said Yuman Fong, M.D., chairman of the City of Hope Surgical Oncology Sangiacomo Family Foundation, who developed CF33.
The three-year trial is designed to enroll patients who have been diagnosed with recurrent metastatic TNBC and whose disease has not been controlled after standard treatment. Study participants will be treated with six doses of drugs injected directly into the tumor over a total of three cycles.
Once the scientists observe increased expression of checkpoints targeting PD-1, PD-L1, or CTLA-4 and an increase in CD8+ immune cells in the patients, they will be able to show that the oncolytic virus activates the immune system against breast cancer. When more of these checkpoint targets are present, currently approved experimental therapies will be better able to “capture” cancer cells and destroy them from within.