The FDA marked a number of firsts Wednesday when it granted accelerated approval to Genentech Inc.'s bladder cancer immunotherapy Tecentriq and Ventana Medical Systems' companion diagnostic.

The approval makes Tecentriq (atezolizumab) the first PD-1/PD-L1 inhibitor approved to treat advanced urothelial carcinoma, the most common type of bladder cancer. And the Ventana PD-L1 (SP142) assay is the first test to detect PD-L1 protein expression levels on tumor-infiltrating immune cells by staining and scoring the cells within the tumor microenvironment.

Although urothelial carcinoma is the fifth most common cancer with nearly 77,000 new cases and more than 16,000 deaths each year, the approval of the personalized cancer immunotherapy and complementary diagnostic is the first major advancement in the treatment of the disease in more than 30 years, according to Genentech and Ventana, which are both part of the Roche Group, of Basel, Switzerland.

Tecentriq will be available in the U.S. within one to two weeks. The drug will launch at a monthly cost of about $12,500, Genentech spokeswoman Emmy Wang told BioWorld Today. The company plans to offer assistance programs for eligible patients whose locally advanced or metastatic bladder cancer has progressed on platinum-based chemotherapy.

While Tecentriq is the first PD-L1 biologic approved by the FDA, it is the latest of the broader class of PD-1/PD-L1 targeted biologics approved by the agency over the past two years. "Products that block PD-1/PD-L1 interactions are part of an evolving story about the relationship between the body's immune system and its interaction with cancer cells," said Richard Pazdur, director of the FDA's Office of Hematology and Oncology Products.

The accelerated approval of Tecentriq, which the FDA had designated as a breakthrough therapy, was supported by a phase II single-arm clinical trial enrolling 310 patients with locally advanced or metastatic urothelial carcinoma. In addition to an objective response rate (ORR) determined by complete or partial shrinkage of tumors, the trial looked at the difference in effect based on positive vs. negative expression of the PD-L1 protein on patients' tumor-infiltrating immune cells.

Results showed that 14.8 percent of all participants experienced at least a partial shrinkage of their tumors, which lasted from 2.1 months to more than 13.8 months at the time of the analysis. However, the ORR was 26 percent in patients classified as positive for PD-L1 expression, compared with 9.5 percent for those who were negative for PD-L1.

"The greater effect in those who were classified as positive for PD-L1 expression suggests that the level of PD-L1 expression in tumor-infiltrating immune cells may help identify patients who are more likely to respond to treatment with Tecentriq," the FDA said. While the companion diagnostic, which uses immunohistochemistry technology to visually enhance and score PD-L1 protein, is not required, it could help doctors determine which patients may benefit most from treatment with the biologic.

The PD-L1 assay is "not a traditional predictive biomarker," Daniel Chen, cancer immunotherapy franchise head at Genentech, told BioWorld Today last year. Instead, it predicts the likelihood that a patient will benefit from PD-1/PD-L1 inhibition as a single agent. With a better understanding of why immunotherapies work, or don't, in an individual patient, a biomarker also can be used to select the best combination therapies. (See BioWorld Today, April 21, 2015.)

Low PD-L1 staining most often means there is no pre-existing immunity in a patient, which suggests that the immune system needs to be shaken awake, while an inability of T cells to infiltrate the tumor might suggest a combination with angiogenesis-targeting drugs, and insufficient immunity could be fought with an additional checkpoint inhibitor.

MORE APPROVALS ON THE WAY?

Other approvals may not be far off for the Roche duo. The FDA granted priority review last month for Tecentriq in locally advanced or metastatic non-small-cell lung cancer that expresses PD-L1, as determined by the companion diagnostic. The drug has an Oct. 19 PDUFA date for that indication, Wang said. Applications for the lung and bladder cancer indications also have been submitted to the EMA, and applications have been filed with regulators in other countries.

Meanwhile, clinical development continues. Tecentriq is undergoing a confirmatory phase III bladder cancer study in which it is being compared with chemotherapy in patients whose cancer has progressed on at least one prior platinum-containing regimen.

In addition, "we are studying Tecentriq in more than 30 ongoing clinical trials across several kinds of cancer, including lung, kidney, breast, colon, skin, bladder and blood cancers," Wang said. Some of the studies are testing potential combinations of atezolizumab with chemotherapy. (See BioWorld Today, Aug. 18, 2015.)

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