Roche has found redemption in a precision medicine approach following an earlier Tecentriq trial flop in a broader bladder cancer population.
Tecentriq helped certain patients with muscle-invasive bladder cancer (MIBC) live longer compared with placebo when used after surgery, according to results from the phase 3 IMvigor011 trial. The PD-L1 inhibitor also outperformed placebo at preventing disease recurrence, metastasis or death on the study’s primary endpoint, disease-free survival.
The comparison—and the administration of Tecentriq or placebo—was made in patients who tested positive for molecular residual disease (MRD) up to 12 months after surgery but stayed free of cancer recurrence on imaging. MRD measures small traces of remaining cancer cells that may not show up as tumors on imaging.
Natera, which developed the circulating tumor DNA test to measure MRD, reported the news Monday. Roche, which sponsors the study, did not announce the readout in a press release. A spokesperson for Roche’s U.S. subsidiary, Genentech, confirmed the hit on both trial endpoints to Fierce Pharma and said data will be shared with the FDA and presented at an upcoming medical meeting.
During Roche’s second-quarter earnings presentation last month, the company listed Tecentriq in ctDNA-positive high-risk MIBC as one of its planned regulatory submissions in 2025.
The improvements by Tecentriq were “statistically significant and clinically meaningful,” according to Natera. The Texas-based company said it plans to finalize its application to the FDA for the ctDNA test, called Signatera, as a companion diagnostic for selecting MIBC patients who may receive Tecentriq as an adjuvant treatment after cystectomy.
“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,” the study’s lead investigator, Thomas Powles, M.D., from Britain’s Barts Cancer Institute, said in a statement Monday.
The positive IMvigor011 readout from an MRD-selective population came more than five years after the IMvigor010 trial comparing adjuvant Tecentriq with simple observation in an unselective group of MIBC patients failed to meet its primary goal of disease-free survival.
The MIBC landscape is no longer the same as it was five years ago. In March, the FDA approved AstraZeneca’s Imfinzi as the first immunotherapy for MIBC. The PD-L1 inhibitor nabbed a perioperative approval for use alongside chemotherapy before surgery and then on its own after surgery.
The regimen mounted a statistically significant 25% reduction in the risk of death compared with neoadjuvant chemo alone followed by surgery, according to results from the phase 3 Niagara trial conducted in a biomarker-unrestricted patient population.
What’s more, word came out last week that the combination of Pfizer and Astellas’ antibody-drug conjugate Padcev and Merck & Co.’s Keytruda also delivered an all-around perioperative win in patients with cisplatin-ineligible MIBC.