Genentech recently announced results from a Phase II study, IMvigor 210, during the 2015 European Cancer Congress, Vienna, Austria.
The trial assessed the use of investigational cancer immunotherapy atezolizumab in individuals with advanced urothelial carcinoma. The results demonstrated that atezolizumab shrank tumors in 27% of patients who had a specific biomarker protein in their tumor cells’ surface called PD-L1 and who had worsened after their first cancer treatment. Side-effects were the same as in other studies of the same treatment.
Atezolizumab is a monoclonal antibody that blocks the activity of PD-L1, specifically on tumor cells and tumor-infiltrating immune cells. PD-L1 suppresses the immune system, which can be useful in conditions such as pregnancy, but it can also contribute to disease as is the case with cancer. Through inhibition of PD-L1, atezolizumab may activate T cells helping the patient’s immune system to fight tumors. The efficiency of this novel immunotherapy greatly relies on the amount of PD-L1 present in tumor cells. “Unlike other biomarkers, there have not been large-scale epidemiological studies of PD-L1 prevalence. However, because of our studies and others we are beginning to gain a better understanding. In mUC, the IMvigor 210 trial showed that approximately 30 percent of people have tumors that express medium to high levels of PD-L1”, Holli Kolkey, Associate Director, Corporate Relations, Genentech, explained in an exclusive interview for Immuno-Oncology News.
According to the National Cancer Institute, bladder cancers such as urothelial carcioma are the sixth most common form of cancer. Men are more likely to get bladder cancer than women. Urothelial carcinoma is the most common form of bladder cancer (90%), with over 74,000 Americans receiving a bladder cancer diagnosis in 2015. Advanced bladder cancer is harder to treat and has a substantially lower survival rate. About 15 percent of those individuals with advanced bladder cancer will live for five years, as opposed to 88 percent when diagnosed in early stages.
Because the study included people with advanced bladder cancer, the results represent a major breakthrough. “These results may represent the first major treatment advancement in advanced bladder cancer in nearly 30 years,” remarked Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are encouraged that responses to atezolizumab were ongoing in the large majority of people when the study results were assessed.”
When asked if atezolizumab could be used in early stages of the disease, as a first line of therapy, Ms. Kolkey told Immuno-Oncology News that, “This year at ECC we presented results from the BIRCH study that included patients who received atezolizumab in the first line. We also have five ongoing Phase III studies of atezolizumab as a first-line treatment in NSCLC. We are also currently studying atezolizumab in multiple treatment settings in advanced cancer, including as a first-line treatment across tumor types, such as triple negative breast cancer. Additionally, we are studying atezolizumab in the early stages of the disease where the goal of treatment is to prevent the cancer from coming back after surgery (adjuvant setting). Currently, we have an adjuvant Phase III study of atezolizumab for both invasive bladder cancer and separately, NSCLC.”
The company will submit results to global health authorities and to the U.S. Food and Drug Administration (FDA) based on atezolizumab’s Breakthrough Therapy Designation. The designation speeds up developmental of treatments for serious diseases, specifically medications that are substantial improvements from what is currently available. “We are discussing results from IMvigor 210 and our lung studies with the FDA, under atezolizumab’s Breakthrough Therapy Designation (BTD), so that we can bring this medicine to people with advanced bladder and lung cancers as soon as possible”, Ms. Kolkey told Immuno-Oncology News.
Genentech is also assessing atezolizumab in a Phase III study, called IMvigor 211, which compares atezolizumab with standard chemotherapy in people with relapsed urothelial carcinoma that became worse after a first treatment. Researchers will also measure PD-L1 status in these patients.
Phase II studies are typically conducted to assess the best dose of a medication to use and to test initial effectiveness and safety, whereas Phase III studies are larger trials that are needed for the eventual approval of a medication. The medication will rapidly advance through clinical trials due to its Breakthrough Therapy Designation, and will hopefully aid in the fight to effectively treat bladder cancer.
