On May 15, 2026, the FDA approved Signatera CDx (Natera, Inc.) as a companion diagnostic device to identify adult patients with MIBC after radical cystectomy who have ctDNA MRD and are therefore candidates for adjuvant treatment with atezolizumab (Tecentriq) or atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza), both manufactured by Genentech. The diagnostic approval was issued simultaneously with the therapeutic approvals. According to the FDA, the application was granted priority review and used the Assessment Aid voluntary submission to facilitate review.
Signatera is a tumor-informed assay. Whole-exome sequencing of resected tumor tissue is used to design a custom multiplex PCR panel of patient-specific somatic variants, which is then applied to plasma to detect residual ctDNA. The CDx authorization required bridging analyses confirming equivalence between the commercial assay and the clinical trial assay used in the supporting study, in addition to analytical performance validation.
Per the approved label, patients who test negative on Signatera CDx after cystectomy should continue serial testing until either a positive result or completion of the 12-month post-surgical testing window. Only patients with a positive ctDNA MRD result are eligible for adjuvant atezolizumab.
Clinical Evidence
The approval was supported by IMvigor011 (NCT04660344), a multicenter, randomized, double-blind, placebo-controlled Phase III trial sponsored by Genentech. Results were presented at the European Society for Medical Oncology (ESMO) Congress 2025 and published in The New England Journal of Medicine in October 2025.
You can read more on the results presented at ESMO 2025 on OncoDaily.
The trial enrolled 761 patients with MIBC who had undergone radical cystectomy with lymph node dissection. All patients underwent serial Signatera ctDNA testing for up to 12 months after surgery during a surveillance phase. Patients who tested ctDNA-positive and remained free of radiographic recurrence (n = 250) were randomized to adjuvant atezolizumab (n = 167) or placebo (n = 83), administered every 4 weeks for up to 12 cycles or one year. Patients who remained persistently ctDNA-negative were not randomized and continued under surveillance.
Efficacy outcomes in the ctDNA-positive randomized population (median follow-up 16.1 months):
- Disease-free survival (DFS): median 9.9 months (95% CI, 7.2–12.7) with atezolizumab versus 4.8 months (95% CI, 4.1–8.3) with placebo (stratified HR 0.64; 95% CI, 0.47–0.87; P = 0.0047).
- Overall survival (OS): median 32.8 months with atezolizumab versus 21.1 months with placebo (HR 0.59; P = 0.0131).
Outcomes in the persistently ctDNA-negative cohort (no adjuvant therapy):
- 24-month DFS rate: 88.4%.
- 24-month OS rate: 97.1%.
The safety profile of atezolizumab in IMvigor011 was consistent with prior reports for this agent, as noted by the trial investigators. The trial did not report head-to-head analytical performance metrics such as sensitivity, specificity, or predictive values from the IMvigor011 dataset itself in the primary publication; the FDA review relied on the bridging analytical validation submitted with the PMA application together with the clinical outcomes data above.
Outlook: A Regulatory Template for MRD-Guided Drug Development
The strategic significance of this approval for the biotech sector is the establishment of a workable template.
Sponsors developing adjuvant or maintenance therapies now have precedent for designing trials in which MRD status functions as:
- An enrichment criterion for trial enrollment.
- A CDx claim in the approved label.
- A reimbursement anchor for serial testing economics.
Regulators have signaled that a sufficiently sensitive, tumor-informed assay — validated through a bridging study to a co-developed therapeutic — can clear PMA review.
What This Means for Stakeholders
- For Natera: Converts a market-leading LDT franchise into a regulated, label-referenced diagnostic embedded in a drug’s prescribing information.
- For competitors: Establishes the performance bar — patient-specific variant tracking with prospectively demonstrated bidirectional clinical utility.
- For the broader oncology biotech ecosystem: Marks the moment when MRD moved from prognostic curiosity to a regulated component of treatment selection.
The next several years will likely see a wave of MRD-stratified label expansions across solid tumors. The Signatera CDx approval is the proof of concept that this category of diagnostic can reach the FDA’s highest bar and the starting point for a redesign of how adjuvant oncology drugs are developed, labeled, and reimbursed.
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Written by: Semiramida Nina Markosyan, Editor, OncoDaily Canada