Natera's Signatera molecular residual disease (MRD) test has demonstrated exceptional survival outcomes in muscle-invasive bladder cancer (MIBC) patients who remained consistently negative during post-surgical surveillance, according to new analysis from the phase III IMvigor011 trial presented at the European Association of Urology Congress 2024 in Paris, France.
Outstanding Survival Rates in MRD-Negative Patients
The analysis evaluated 171 high-risk MIBC patients who entered screening for the IMvigor011 study and remained MRD-negative throughout the surveillance window. Results showed remarkable survival outcomes, with overall survival (OS) rates of 100% at 12 months and 98% at 18 months among patients who remained serially MRD-negative.
Disease-free survival (DFS) rates were similarly impressive, reaching 92% at 12 months and 88% at 18 months in patients who maintained MRD negativity during surveillance testing.
Implications for Treatment Personalization
Based on these findings, investigators concluded that patients who remain MRD-negative on serial testing may be spared from adjuvant treatment, representing a significant advancement in personalized cancer care.
"IMvigor011 is an important randomized study that is designed to address a critical unmet need for the more than 35,000 patients a year diagnosed with muscle-invasive bladder cancer," said John Simmons, vice president, BioPharma at Natera. "We believe the results of this trial will further demonstrate how Signatera can help personalize treatment decisions and improve outcomes for bladder cancer patients."
Trial Design and Methodology
The IMvigor011 study, sponsored by Genentech, is a global, double-blind, randomized, Phase III trial involving high-risk MIBC patients who undergo serial testing with Signatera for up to 12 months post cystectomy. Patients who test Signatera MRD-positive at any point during the 12-month surveillance window are randomized to receive the anti-PDL1 atezolizumab (Tecentriq) versus placebo. Those who remain Signatera-negative at completion of the testing window are not randomized but continue radiographic imaging surveillance.
Supporting Evidence from Previous Studies
These findings build upon previously published data from the phase III IMvigor010 trial, which showed that patients who tested Signatera MRD-positive after radical cystectomy received significant benefit from adjuvant immunotherapy with atezolizumab, while Signatera-negative patients derived no significant benefit from adjuvant therapy. The IMvigor010 results, published in Nature, demonstrated that ctDNA-positive patients benefited from adjuvant atezolizumab compared with observation, with improved disease-free survival (HR, 0.58; 95% CI, 0.43-0.79; P = .0024) and overall survival (HR, 0.59; 95% CI, 0.41-0.86).
Regulatory Progress
Natera submitted the first module of its premarket approval application to the U.S. Food and Drug Administration (FDA) for Signatera as a companion diagnostic assay for patients with MIBC in October 2023. The company anticipates that the full IMvigor011 trial readout could serve as the basis for this FDA companion diagnostic submission.
"This milestone reflects the significant efforts of our team in developing an FDA-grade quality and manufacturing system, a strong foundation designed to support future regulatory submissions across disease indications for Signatera and across product lines," said Steve Chapman, chief executive officer at Natera, regarding the FDA submission.
The Signatera test is currently available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer, ovarian cancer and muscle-invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor.
