Dr Bellmunt on Future Directions With ctDNA-Guided Immunotherapy in Urothelial Cancer

“[IMvigor011] will inform the basis for other trials that are already ongoing. For example, we have the MODERN trial where patients with ctNDA positivity are assigned to receive immunotherapy.”

Joaquim Bellmunt, MD, PhD, the director of the Bladder Cancer Center and a senior physician at Dana-Farber Cancer Institute, as well as an associate professor of medicine at Harvard Medical School, discussed how findings from the phase 3 IMvigor011 trial (NCT04660344) of circulating tumor DNA (ctDNA)–guided adjuvant atezolizumab (Tecentriq) in patients with muscle-invasive bladder cancer (MIBC) will inform future studies.

Findings from IMvigor011 presented during the 2025 ESMO Congress showed that patients who were ctDNA positive after surgery who received adjuvant atezolizumab (n = 167) achieved investigator-assessed disease-free survival (DFS; HR, 0.64; 95% CI, 0.47-0.87; P = .0047) and overall survival (OS; HR, 0.59; 95% CI, 0.39-0.90; P = .0131) benefits vs placebo. These data will be useful in informing future clinical trials, Bellmunt began. For example, in the phase 2/3 MODERN study (NCT05987241), patients with urothelial cancer who were positive for ctDNA following surgery were treated with nivolumab (Opdivo) with or without relatlimab (Opdualag). In contrast with IMvigor011, this study is asking the additional question of how to optimize the ctDNA-guided therapy, he added. Findings from MODERN will help to determine if an adjuvant immunotherapy doublet can provide additional benefit for this patient population, he concluded.

In order to be eligible for MODERN, patients must be at least 18 years of age, have an ECOG performance status of 0 to 2, have received no postoperative/adjuvant systemic therapy after radical surgery, have received no adjuvant radiation after radical surgery, and have undergone no treatment with any other type of investigational agent at 4 weeks or less prior to enrollment. The primary end points are ctDNA negativity, OS, and DFS. Secondary end points include safety, incidence of ctDNA positivity, and lead time for ctDNA positivity conversion.