FDA Grants Priority Review to Keytruda for Non-Muscle Invasive Bladder Cancer

December 3, 2019

The FDA has granted a priority review to a supplemental biologics license application (sBLA) for Keytruda (pembrolizumab), an anti-PD-1 immunotherapy, for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC), according to Merck, the drug’s manufacturer.

The FDA has granted a priority review to a supplemental biologics license application (sBLA) for Keytruda (pembrolizumab), an anti-PD-1 immunotherapy, for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC), according to Merck, the drug’s manufacturer.

The priority review will speed up the timeline by which the FDA will review and potentially approve the drug for this patient population.

In particular, Merck seeks approval for the regimen (which would be Keytruda alone) to treat those who didn’t respond to BCG therapy and whose disease is classified as high-risk NMIBC with carcinoma in-situ with or without papillary tumors who are ineligible for or have elected not to undergo cystectomy.

“Patients with high-risk, non-muscle invasive bladder cancer sometimes make an informed decision to decline, or are medically ineligible for radical cystectomy, and there are currently limited non-surgical treatment options approved by the FDA for these patients who are BCG-unresponsive,” Roy Baynes, M.D., Ph.D., chief medical officer, Merck Research Laboratories, said in a press release.

This application is based on results from the phase 2 KEYNOTE-057 trial, which will be discussed at the FDA’s Oncologic Drugs Advisory Committee (ODAC) meeting on Dec. 17. Moreover, data from this trial were first presented at the European Society for Medical Oncology (ESMO) 2018 Congress.

In the trial, Keytruda showed encouraging activity in patients with high-risk BCG-unresponsive carcinoma in situ with or without papillary tumors and a safety profile consistent with those previously seen.

A cohort of 103 patients received 200 mg of Keytruda every three weeks for 24 months or until recurrence, progression, or unacceptable side effects occurred. Patients with high-risk NMIBC or progressive disease during treatment were required to stop treatment. The primary end point was complete response rate (CRR), which the National Cancer Institute (NCI) defines as, “disappearance of all signs of cancer in response to treatment.”

Key secondary end points were duration of response and safety.

The three-month CRR was 38.8% by central assessment. Among 40 patients who experienced a complete response (CR) at three months, 72.5% maintained CR at last follow-up and median CR duration had not been reached. Overall, 80.2% of patients had a CR duration of six months or longer.

Treatment-related side effects occurred in 65 patients (63.1%), with the most frequent being pruritus (scratch/itching; 10.7%), fatigue (9.7%), diarrhea (8.7%), hypothyroidism (5.8%), and maculopapular rash (5.8%). Grade 3/4 treatment-related AEs occurred in 13 patients (12.6%), and one death was considered treatment-related. Immune-mediated AEs occurred in 19 patients (18.4%).

A phase 2 clinical trial to study the efficacy and safety of Keytruda (MK-3475) in patients with high-risk NMIBC unresponsive to BCG therapy, conducted by Merck, is currently recruiting for a cohort of 260 participants. Primary end points for this trial are CRR and disease-free survival rate, and the key secondary end point is duration of response.

The agency set a Prescription Drug User Fee Act (PDUFA) for January 2020, based on priority review, meaning that the FDA must make its decision on the drug’s approval by the end of the month.


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