Merck & Co has filed for approval of its checkpoint inhibitor Keytruda for both first- and second-line use in bladder cancer in the US.
The filing comes shortly after Bristol-Myers Squibb bagged US approval for its checkpoint inhibitor Opdivo (nivolumab) as a second-line treatment for bladder cancer, with both drugs chasing Roche’s Tecentriq (atezolizumab) – the first immuno-oncology drug to be approved for that form of cancer.
With both Opdivo and Tecentriq approved for second-line use in patients who have progressed despite cisplatin therapy, Merck has a chance of grabbing an advantage in the first-line setting. Roche got a priority review from the FDA for its first-line application last month.
Keytruda has been filed in the first-line setting approval for use in patients with locally advanced or metastatic urothelial cancer (mUC) who are ineligible for cisplatin-containing therapy, while second-line use is being targeted towards these patients with disease progression on or after platinum-containing chemotherapy.
The FDA has previously given Keytruda a priority review both the first- and second-line indications on the strength of the results of the phase II KEYNOTE-052 and the phase III KEYNOTE-045 trials, respectively. It is due to deliver a verdict on both filings by 14 June.
Bladder cancer affects almost 400,000 people a year and kills around 150,000, but has proved to be remarkably resistant to new drug therapy. Prior to the advent of immuno-oncology drugs, there had been no new treatments for patients with metastatic bladder cancer who progress despite platinum-based chemotherapy for 30 years.
The standard of care remains cisplatin, but around half of all patients are not eligible for treatment with that form of chemotherapy. Meanwhile, cisplatin remains only modestly effective in patients who can take the drug.
In the KeyNote-045 trial Keytruda was more effective than chemotherapy at extending patients’ lives when given as a second-line therapy, while KEYNOTE-052 showed an overall response rate of 24% among cisplatin-ineligible patients – with and without PD-L1 expression – who were treated initially with Keytruda. Merck’s drug achieved a slightly lower response rate than chemotherapy in that setting.