Roche's checkpoint inhibitor fails pivotal urothelial cancer trial Phase 3 trial shows no effect on disease-free survival and misses its primary endpoint
A phase 3 trial of Roche’s checkpoint inhibitor Tecentriq (atezolizumab) in muscle-invasive urothelial cancer (MIUC) has missed its primary endpoint.
Tecentriq, an anti-PD-L1 antibody, ceded a sizeable headstart to rival checkpoint inhibitors Keytruda and Opdivo, which are sold by Merck and Bristol-Myers Squibb, respectively. Since winning its first approval in the US in 2016, Roche, in collaboration with its Genentech subsidiary, has worked to close the gap by extending the Tecentriq label into a clutch of additional indications.
MIUC offered Roche an opportunity to carve out a new market for checkpoint inhibitors. While the treatment of urothelial carcinoma and, more recently, non-muscle-invasive bladder cancer (NMIBC) is being changed by checkpoint inhibitors, a mix of surgery, chemotherapy and radiotherapy remains the standard option for patients with MIUC.
Roche wanted to add Tecentriq to the therapeutic toolkit available to physicians, leading it to run a phase 3 trial that randomised around 800 people to receive the checkpoint inhibitor or no medical intervention after undergoing surgical resection. The goal was to show Tecentriq reduces the risk of the recurrence or spread of the disease, which happens in around half of surgically resected patients within two years of the procedure.
However, Roche found administering intravenous cycles of Tecentriq for up to one year after the surgery had no effect on disease-free survival, causing the trial to miss its primary endpoint.
In disclosing the setback, Levi Garraway, chief medical officer at Roche, said it is “very difficult” to cut the risk of MIUC recurring after surgery and expressed disappointment that the drug was “not able to significantly prolong disease-free survival”. Despite that blow, Garraway and Roche are continuing to explore the use of Tecentriq in early cancers.
“We remain committed to exploring the potential benefits of immunotherapy for more people with early cancers,” Garraway said in a statement.
Generating positive clinical data on Tecentriq in those settings would boost Roche’s effort to carve out a niche in the competitive checkpoint inhibitor space. That effort has enjoyed some success.
Despite trailing Keytruda and Opdivo to market, Roche has grown Tecentriq into a blockbuster drug, generating sales of more than $500m (€450m) in the third quarter alone. Roche attributed the 146% growth in sales of the drug over the first nine months of last year to approvals in first-line small cell lung cancer and triple-negative breast cancer, indications in which the checkpoint inhibitor came to market ahead of its rivals.