The phase III IMvigor011 clinical trial has achieved positive topline results, demonstrating that circulating tumor DNA (ctDNA) testing can effectively guide adjuvant immunotherapy decisions in muscle-invasive bladder cancer (MIBC) patients. The study, sponsored by Genentech and utilizing Natera's Signatera ctDNA test, represents a potential paradigm shift in post-surgical bladder cancer management.
Trial Design and Patient Population
IMvigor011 enrolled approximately 760 patients with MIBC in its surveillance phase, making it the first prospective phase III study in this indication to employ a personalized, ctDNA molecular residual disease (MRD)-guided approach. Patients underwent serial Signatera testing for up to 12 months following surgery to detect molecular residual disease in the bloodstream.
The trial's innovative design randomized only Signatera-positive patients who remained free of cancer recurrence on imaging to receive either atezolizumab (Tecentriq®) or placebo. Treatment was administered every 4 weeks for 12 cycles or up to one year. Patients who consistently tested Signatera-negative were not randomized to treatment but continued surveillance with radiographic imaging and ctDNA MRD testing.
Significant Survival Improvements
Topline results demonstrated statistically significant and clinically meaningful improvements in both disease-free survival and overall survival for Signatera-positive patients treated with atezolizumab compared to placebo. These findings support the use of ctDNA testing to identify patients most likely to benefit from adjuvant immunotherapy.
"The results of IMvigor011 are very significant, opening the door for a new treatment paradigm for bladder cancer patients who are positive for recurrence on a molecular level but have no evidence of disease on imaging," said Professor Thomas Powles, lead principal investigator of the study at Barts Cancer Institute QMUL.
Excellent Outcomes for ctDNA-Negative Patients
A preliminary analysis of Signatera-negative patients, presented at the European Association of Urology in April 2024, revealed excellent outcomes without adjuvant treatment. Among 171 patients who remained Signatera-negative during the surveillance window, overall survival rates reached 100% at 12 months and 98% at 18 months. Disease-free survival rates were 92% at 12 months and 88% at 18 months after surgery.
These findings suggest that patients with negative ctDNA results may safely avoid adjuvant therapy and its associated toxicities while maintaining excellent clinical outcomes.
Clinical Impact and Regulatory Path
"Importantly, IMvigor011 could change how resectable bladder cancer is managed for the tens of thousands of patients diagnosed with MIBC each year," said Alexey Aleshin, general manager of oncology and corporate chief medical officer at Natera.
Based on these positive results, Natera plans to finalize its premarket approval application to the U.S. Food and Drug Administration for Signatera as a companion diagnostic for selecting patients with MIBC to be treated with atezolizumab after cystectomy.
The company expects to present detailed trial data at an upcoming medical conference, which will provide the medical community with comprehensive insights into this novel precision medicine approach for bladder cancer management.
