Dr Bellmunt on the Design of the IMvigor011 Trial of ctDNA-Guided Adjuvant Atezolizumab in MIBC

“We screened [approximately] 800 patients for this trial and saw that [approximately] half of the patients were ctDNA positive after surgery. We were able to screen patients for at least 6 months.”

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 the design of the phase 3 IMvigor011 trial (NCT04660344) of circulating tumor DNA (ctDNA)–guided adjuvant atezolizumab (Tecentriq) for the treatment of patients with muscle-invasive bladder cancer (MIBC).

IMvigor011 enrolled patients with MIBC who underwent radical cystectomy within 6 to 24 weeks of screening and had histologically confirmed (y)pT2-T4aN0M0 or (y)pT0-T4aN+M0 disease and no evidence of radiographic disease progression. Prior neoadjuvant therapy was permitted, and patients were required to have an ECOG performance status of 0 to 2.

Following surgery, patients were screened for ctDNA, Bellmunt explained. Patients who were positive for ctDNA were randomly assigned 2:1 to receive adjuvant atezolizumab or placebo, he continued. A total of 250 patients were included in the study, he added. Atezolizumab was administered at 1680 mg once every 4 weeks for up to 1 year.

The primary end point was investigator-assessed disease-free survival (DFS), Bellmunt said. Overall survival was the key secondary end point, he concluded.

At baseline, the median age among patients positive for ctDNA was 69 years (range, 42-87) in the atezolizumab arm (n = 167) vs 67 years (range, 44-84) in the placebo arm (n = 83). Most patients in both groups were male (84.4% vs 80.7%), were European (60.5% vs 59.0%), had an ECOG performance status of 0 (67.7% vs 63.9%), had PD-L1 expression of less than 5% (64.7%; 63.9%), did not receive neoadjuvant chemotherapy (52.1% vs 60.2%), had positive nodal status (57.5% vs 57.8%), were a maximum of 20 weeks removed from cystectomy to first positive ctDNA sample (70.1% vs 71.1%), and were ctDNA positive per their initial test (59.3% vs 59.0%).

Following surgery, patients were screened for ctDNA, Bellmunt explained. Patients who were positive for ctDNA were randomly assigned 2:1 to receive adjuvant atezolizumab or placebo, he continued. A total of 250 patients were included in the study, he added. Atezolizumab was administered at 1680 mg once every 4 weeks for up to 1 year.

The primary end point was investigator-assessed disease-free survival (DFS), Bellmunt said. Overall survival was the key secondary end point, he concluded.

At baseline, the median age among patients positive for ctDNA was 69 years (range, 42-87) in the atezolizumab arm (n = 167) vs 67 years (range, 44-84) in the placebo arm (n = 83). Most patients in both groups were male (84.4% vs 80.7%), were European (60.5% vs 59.0%), had an ECOG performance status of 0 (67.7% vs 63.9%), had PD-L1 expression of less than 5% (64.7%; 63.9%), did not receive neoadjuvant chemotherapy (52.1% vs 60.2%), had positive nodal status (57.5% vs 57.8%), were a maximum of 20 weeks removed from cystectomy to first positive ctDNA sample (70.1% vs 71.1%), and were ctDNA positive per their initial test (59.3% vs 59.0%).