NEW YORK – Genentech on Wednesday began a Phase III trial of its PD-L1 inhibitor atezolizumab (Tecentriq) in bladder cancer using Natera's molecular residual disease (MRD) test Signatera as a companion diagnostic.
The IMvigor011 study is evaluating adjuvant atezolizumab versus placebo in patients with PD-L1-positive, muscle invasive bladder cancer. The trial will enroll about 500 participants who are MRD-positive within 20 weeks post-surgery based on Natera's ctDNA test. Patients will receive atezolizumab or placebo within the trial for 12 cycles or up to one year, and researchers are primarily interested in patients' disease-free survival in the two arms.
In a previous Phase III study of atezolizumab as an adjuvant treatment versus observation in early-stage bladder cancer, 37 percent of patients were MRD-positive according to Signatera after surgery. In this group, those on atezolizumab after surgery fared better than those who received nothing, with a median disease-free survival of 5.9 months versus 4.4 months, and a median overall survival of 25.8 months versus 15.8 months, respectively. Meanwhile, 63 percent of patients who were MRD-negative by Signatera had no benefit from adjuvant atezolizumab treatment.
"There is a strong unmet need in this population, as bladder cancer patients with residual disease post-surgery are known to be at the highest risk of recurrence," Thomas Powles, professor at Barts Cancer Institute and principal investigator of the latest study, said in a statement. "The Signatera MRD test offers a personalized, real-time diagnostic to identify bladder cancer patients who need additional therapy and may benefit from adjuvant treatment with Tecentriq."
This week, Roche voluntarily withdrew atezolizumab as an option for bladder cancer patients in the US who have previously received platinum chemotherapy. The move was triggered by a review by the US Food and Drug Administration of therapies it has granted accelerated approval, a designation that requires drugmakers show further evidence of benefit to keep treatments on the market. Atezolizumab is approved in the US for first-line metastatic bladder cancer, PD-L1-positive lung cancer, liver cancer, PD-L1-positive triple-negative breast cancer, and BRAF V600 mutation-positive melanoma.