Natera has submitted Signatera to Japan's PMDA for approval as a companion diagnostic in muscle-invasive bladder cancer.
Natera, Inc. has submitted an application to Japan's Pharmaceuticals and Medical Devices Agency (PMDA) for approval of the Signatera test as a companion diagnostic in muscle-invasive bladder cancer (MIBC).1
The submission is supported by data from the phase 3 IMvigor011 trial (NCT04660344), a randomized, double-blind study of ctDNA-guided adjuvant atezolizumab (Tecentriq) vs placebo following radical cystectomy in patients with high-risk MIBC.¹,² The application follows Signatera's PMDA approval in colorectal cancer (CRC) in June 2026, when the test became the first PMDA-approved molecular residual disease (MRD) assay in Japan.¹
In the underlying trial, ctDNA-guided adjuvant atezolizumab produced statistically significant improvements in investigator-assessed disease-free survival (DFS; HR, 0.64; 95% CI, 0.47-0.87; P = .005) and overall survival (OS; HR, 0.59; 95% CI, 0.39-0.90; P = .01) vs placebo in patients who tested ctDNA positive after cystectomy, while patients who remained persistently ctDNA negative had a low risk of recurrence or death without adjuvant treatment, according to findings published in the New England Journal of Medicine.²
"Signatera is a proven tool in bladder cancer management, and this submission reflects our commitment to bringing precision diagnostics to patients in Japan," Alexey Aleshin, MD, corporate chief medical officer and general manager of oncology at Natera, stated in a news release.¹ “We look forward to engaging with the PMDA and to improving outcomes for patients around the world.”
IMvigor011 was a global, randomized, double-blind phase 3 trial evaluating a ctDNA-guided adjuvant immunotherapy strategy in patients with high-risk MIBC following radical cystectomy.²
Patients with no radiographic evidence of disease after surgery underwent serial ctDNA monitoring for up to 1 year; those who tested ctDNA positive and remained disease-free were randomly assigned to receive atezolizumab or placebo, while patients who remained persistently ctDNA negative were followed in a surveillance cohort without randomized treatment. The trial's design was intended to test whether MRD status, as detected by Signatera, could identify patients most likely to benefit from adjuvant checkpoint inhibition while sparing ctDNA-negative patients from unnecessary treatment.
The primary end point was investigator-assessed DFS. OS was assessed as a secondary end point.
The PMDA application builds on the
Signatera MRD-guided adjuvant atezolizumab also holds a Category 1 recommendation in the NCCN Clinical Practice Guidelines for Bladder Cancer.
