With the help of DNA testing company Natera and its personalized molecular residual disease (MRD) blood test Signatera, Roche’s PD-L1 inhibitor Tecentriq has chalked up its eleventh U.S. indication in the form of a new bladder cancer approval.
Tecentriq and subcutaneous Tecentriq Hybreza can now be used as an adjuvant treatment for adult patients with muscle-invasive bladder cancer (MIBC) who have circulating tumor DNA molecular residual disease (ctDNA MRD) following a cystectomy, as identified by Signatera.
“Combining our cancer immunotherapy Tecentriq with state-of-the-art MRD testing allows more precise identification of patients who are candidates for intervention and those who might safely avoid unnecessary treatment,” Roche’s chief medical officer and head of global product development, Levi Garraway, M.D., Ph.D., said in a company release. “We look forward to delivering this first-of-its-kind ctDNA-guided regulatory approval to bladder cancer physicians and patients in the U.S.”
A bladder removal surgery (cystectomy) paired with chemotherapy is typically used as the go-to standard of care for patients diagnosed with MIBC, but nearly half of the over 150,000 patients worldwide who undergo the procedure each year see their cancer return after surgery, according to Roche.
Typically, doctors will rely on tumor staging to determine if a patient may need treatment following surgery, but Natera’s Signatera assay can spot molecular evidence of cancer in the blood before it becomes visible through standard imaging.
With this first FDA approval of a ctDNA-guided therapy, clinicians will be able to selectively offer treatment to those who are at the greatest risk of disease recurrence and can most benefit from immunotherapy, clearing up post-surgical uncertainty and allowing many to safely avoid further treatment, the Bladder Cancer Advocacy Network’s CEO, Meri-Margaret Deoudes, explained in Roche’s release.
The FDA cleared both Tecentriq and companion diagnostic Signatera at the same time after reviewing data from Roche’s late-stage IMvigor011 study, which was the first prospective phase 3 study to significantly improve survival in MIBC through a ctDNA-guided approach.
After 761 prospective trial participants underwent serial ctDNA testing for over a year post-surgery, 250 were evaluated on either Tecentriq or placebo.
Across the 250 patients deemed eligible for the trial’s treatment phase based on the assay, Tecentriq cut the risk of disease recurrence or death by 36%, reducing the risk of death specifically by 41%.
The trial results suggested that the treatment and diagnostic duo could “change how resectable bladder cancer is managed for the tens of thousands of patients diagnosed with MIBC each year,” Natera’s corporate chief medical officer and general manager of oncology, Alexey Aleshin, M.D., said at the time.
Roche had switched up its strategy for Tecentriq in MIBC after the study’s predecessor, IMvigor010, failed to meet its primary goal of disease-free survival in an unselective group of MIBC patients back in 2020. Now, the company says that Natera’s ctDNA-guided therapy, which it helped introduce, is being investigated in other types of cancer, as well.
The precision medicine aspect to Tecentriq’s latest approval could give it a unique advantage in the crowded bladder cancer treatment landscape. Tecentriq itself was the first PD-L1 inhibitor to open the door in the disease area with its first-in-class 2016 nod to treat certain patients with urothelial carcinoma, a common type of bladder cancer. Since then, the drug has widened its reach to an array of cancer types, including breast cancer and lung cancer.
Meanwhile, other PD-L1 inhibitors have been making plenty of headway in the bladder cancer space. AstraZeneca’s Imfinzi became the first immunotherapy to win a perioperative label in MIBC last year, while Bristol Myers Squibb’s Opdivo nabbed a post-surgical approval in 2021. In addition, the pairing of Merck’s star PD-L1 Keytruda and Pfizer’s antibody-drug conjugate Padcev has been on a hot streak lately, with multiple trial wins in different bladder cancer populations.