FDA clears Keytruda/Padcev regimen for bladder cancer

The combination of Merck & Co’s checkpoint inhibitor Keytruda and Seagen/Astellas’ antibody-drug conjugate Padcev has been approved by the FDA as an alternative to chemotherapy for patients with bladder cancer.

The two drugs have been given accelerated clearance as initial therapy for adults with locally advanced or metastatic urothelial cancer (la/mUC) – the most common form of bladder cancer – who aren’t candidates for standard first-line treatment with platinum-based drugs.

The filing for the regimen was based on the results of a subgroup of patients in the KEYNOTE-869 or EV-301 basket trial, which paired Padcev (enfortumab vedotin) with a number of other drugs in this type of cancer.

The EV-103 trial, which compared Padcev on its own or in combination with Keytruda (pembrolizumab), revealed an overall response rate (ORR) of 68%, including 12% complete responses, said the FDA.

In Cohort K the median duration of response was not yet reached. Data from another open-label arm (Cohort A) and a dose-escalation group showed a median duration of response of 22 months. Typically, alternative chemo regimens for patients with mUC who are unable to tolerate platinum drugs like cisplatin have been as little as eight to 10 months.

Nectin-4 directed ADC Padcev has been approved since 2019 as a single agent for use in patients with la/mUC who have previously received a PD-1/PD-L1 inhibitor, such as Keytruda, as well as platinum-containing chemotherapy, or who are ineligible for cisplatin treatment.

The new approval brings the ADC into the front-line setting, and also extends the indications for Keytruda, which has been cleared for first-line use in cisplatin-ineligible patients, as well as for patients whose disease progresses after first-line chemo.

The accelerated approval means Padcev and Keytruda can be used for these patients for the time being, but will have to show a benefit as first-line therapy in the confirmatory EV-302 study, which is due to read out later this year.

If the results of this trial are positive, the combination could replace chemo as the standard-of-care option for these patients, although when it was designed the treatment landscape was a little different, as at that time EMD Serono/Pfizer’s PD-1 inhibitor Bavencio (avelumab) had not yet been approved for first-line maintenance therapy of mUC.

Analysts have previously suggested that a first-line mUC indication could grow Padcev’s sales towards the $2.5 billion mark. Astellas estimates there are approximately 8,000 to 9,000 patients in the US with la/mUC who are not eligible for cisplatin-based chemo.