The FDA has granted a priority review to a supplemental biologics license application (sBLA) for pembrolizumab (Keytruda), an anti-PD-1 therapy, 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.1
In particular, Merck seeks approval for the monotherapy regiment to treat those with BCG-unresponsive, 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, MD, PhD, chief medical officer, Merck Research Laboratories, said in a press release.
This application is based on results from the phase II KEYNOTE-057 trial, which will be discussed at the FDA’s Oncologic Drugs Advisory Committee (ODAC) meeting to be held on December 17. Moreover, data from this trial were first presented at the European Society for Medical Oncology (ESMO) 2018 Congress.
In the phase II KEYNOTE-057 trial, pembrolizumab had 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.2
A cohort of 103 patients received 200 mg of pembrolizumab every 3 weeks for 24 months or until recurrence, progression, or unacceptable toxicity. Patients with high-risk NMIBC or progressive disease during treatment were required to discontinue. The primary end point was complete response rate (CRR). Key secondary end points were duration of response and safety.
The 3-month CRR rate was 38.8% (95% CI; 29.4%-28.9%) by central assessment. Among 40 patients who experienced a complete response (CR) at 3 months, 72.5% maintained CR at last follow-up (median follow-8-, 14 months; range 4.0-26.3) and median CR duration had not been reached (range 0+ to 14.1+ months). Overall, 80.2% of patients had a CR duration of ≥6 months.
Treatment-related adverse events (AEs) occurred in 65 patients (63.1%), with the most frequent being pruritus (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 1 death was considered treatment-related. Immune-mediated AEs occurred in 19 patients (18.4%).
A phase II clinical trial to study the efficacy and safety of pembrolizumab (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.
1. FDA Grants Priority Review to Merck’s Supplemental Biologics License Application (sBLA) for KEYTRUDA® (pembrolizumab) in Certain Patients with High-Risk, Non-Muscle Invasive Bladder Cancer (NMIBC) [news release]. Kenilworth, NJ. Published December 2, 2019. mrknewsroom.com/news-release/oncology/fda-grants-priority-review-mercks-supplemental-biologics-license-application-s. Accessed December 2, 2019.
2. Balar AV, Kulkarni GS, Uchio EM, et al. Keynote 057: Phase II trial of Pembrolizumab (pembro) for patients (pts) with high-risk (HR) nonmuscle invasive bladder cancer (NMIBC) unresponsive to bacillus calmette-guérin (BCG). Journal of Clinical Oncology. doi:10.1200/JCO.2019.27.7_suppl.350