The phase III IMvigor011 trial demonstrates that Signatera ctDNA testing can successfully identify bladder cancer patients who benefit from adjuvant atezolizumab immunotherapy, with Signatera-positive patients showing statistically significant improvements in both disease-free and overall survival. This represents the first prospective phase III study using personalized ctDNA molecular residual disease (MRD) guidance in muscle-invasive bladder cancer.
Study Design & Population
- Phase III randomized, placebo-controlled trial sponsored by Genentech
- Approximately 760 patients with muscle-invasive bladder cancer (MIBC) enrolled in surveillance phase
- Serial Signatera ctDNA testing performed for up to 12 months post-surgery
- Signatera-positive patients randomized to atezolizumab or placebo (12 cycles over one year)
- Signatera-negative patients followed with imaging and ctDNA testing without randomization
Key Findings
- Primary endpoints: Statistically significant and clinically meaningful improvement in disease-free survival and overall survival for Signatera-positive patients treated with atezolizumab
- Signatera-negative patients (171 patients): 100% overall survival at 12 months, 98% at 18 months; 92% disease-free survival at 12 months, 88% at 18 months
- Treatment approach: Atezolizumab administered every 4 weeks for patients testing Signatera-positive
Clinical Implications
- Paradigm shift: Opens door for treating patients with molecular evidence of recurrence but no imaging evidence of disease
- Precision medicine approach: ctDNA MRD testing can guide adjuvant immunotherapy decisions in resectable bladder cancer
- Treatment optimization: Signatera-negative patients may avoid unnecessary adjuvant treatment while maintaining excellent outcomes
Limitations
- Detailed data pending: Full results to be presented at upcoming medical conference
- Regulatory approval: Natera finalizing premarket approval application to FDA for Signatera as companion diagnostic
- Long-term follow-up: Extended survival data may be needed to confirm durability of benefit
