FDA approves atezolizumab for ctDNA

The U.S. Food and Drug Administration on May 15 approved Genentech’s Tecentriq, or atezolizumab, for adults with muscle-invasive bladder cancer after cystectomy whose blood tests show circulating tumor DNA molecular residual disease, according to the drug’s updated label and company statements. The approval also covers Tecentriq Hybreza, the subcutaneous formulation of atezolizumab and hyaluronidase-tqjs. The agency said treatment selection should be based on detection of ctDNA MRD in plasma through serial testing between six weeks and one year after cystectomy. Natera’s Signatera CDx was approved the same day as the companion diagnostic for identifying eligible patients. ### Why is this approval different from earlier bladder-cancer immunotherapy use? The May 15 decision ties an adjuvant immunotherapy label directly to a post-surgical blood-based molecular residual disease test. Genentech said it is the first approved ctDNA MRD-guided therapy in the United States, and Natera said Signatera CDx is the first companion diagnostic approval in blood-based MRD. (accessdata.fda.gov) The Tecentriq label specifies that patients with muscle-invasive bladder cancer should be selected for treatment as a single agent based on detection of ctDNA MRD in plasma via serial testing after cystectomy. Urology Times reported that the FDA-authorized assay requirement applies to both the intravenous and subcutaneous formulations approved in this setting. ### Which patients are eligible for the drug? (gene.com) Adults with muscle-invasive bladder cancer are eligible after cystectomy if they have ctDNA MRD detected by an FDA-authorized test. The label places the testing window between six weeks and one year after surgery, making serial surveillance part of the approved treatment pathway. Genentech said the eligible population is patients whose residual disease is identified by Natera’s Signatera CDx personalized MRD assay. (accessdata.fda.gov) Meri-Margaret Deoudes, chief executive of the Bladder Cancer Advocacy Network, said the approach could help doctors identify patients at higher risk of recurrence while allowing others to avoid additional treatment. ### What evidence did the FDA use? The approval was based on the phase 3 IMvigor011 trial. Genentech said the study showed Tecentriq cut the risk of disease recurrence or death by 36% and reduced the risk of death by 41% in patients with detectable ctDNA MRD identified through serial testing within a year of cystectomy. Urology Times reported more detailed results from IMvigor011, including median disease-free survival of 9.9 months with atezolizumab versus 4.8 months with placebo, and median overall survival of 32.8 months versus 21.1 months. (gene.com) The publication also said grade 3 or 4 treatment-related adverse events occurred in 7.3% of treated patients versus 3.6% with placebo. ### Why does Signatera matter in the approval? Natera’s Signatera CDx was approved as the companion diagnostic used to identify post-cystectomy patients with ctDNA MRD who may receive atezolizumab. That gives the diagnostic a formal role in deciding who gets the drug, rather than simply monitoring disease risk. Thomas Powles, lead principal investigator of IMvigor011, said in Natera’s announcement that the trial and approval showed MRD can guide when to treat and whom to treat more precisely. (urologytimes.com) Levi Garraway, Genentech’s chief medical officer, said combining Tecentriq with MRD testing allows more precise identification of patients who are candidates for intervention. ### What happens next in practice? U.S. oncologists and urologists now have an FDA-approved pathway to use serial ctDNA testing after cystectomy and start adjuvant atezolizumab only if molecular residual disease is detected. The label and companion diagnostic approval mean laboratories, clinicians and payers will need to incorporate the FDA-authorized test into post-surgical care decisions for this population. (businesswire.com) May 15 is the operative approval date for both products, and Genentech said the decision marks Tecentriq’s eleventh U.S. indication. Natera said Signatera already has Medicare coverage across multiple cancer types, but this bladder-cancer companion diagnostic approval gives the assay a defined role in selecting patients for adjuvant treatment after surgery. (gene.com) (accessdata.fda.gov)