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Pembrolizumab Granted Priority Review for Treatment of Patients With NMIBC

Nichole Tucker
Published Online:3:15 PM, Mon December 2, 2019
The FDA has granted priority review to a new supplemental Biologics License Application (sBLA) for pembrolizumab (Keytruda), for which Merck is seeking approval for the treatment of patients with Bacillus Calmette-Guerin (BCG)-unresponsive, high-risk, non-muscle invasive bladder cancer (NMIBC) with carcinoma-in-situ (CIS) with or without papillary tumors who are either ineligible for cystectomy or have chosen not to undergo the procedure, according to a press release from Merck.

The submission of this sBLA was brought on by results phase II KEYNOTE-057 trial, which were originally presented at the 2018 European Society for Medical Oncology (ESMO) Congress. Merck plans to present further data to the FDA’s Oncologic Drugs Advisory Committee (ODAC) on December 17.

The most recent data from KEYNOTE-057 were presented at the 2019 American Society for Clinical Oncology (ASCO) Annual Meeting and showed a complete response (CR) rate of 40.2% (95% CI 30.6%-50.4%) at 3 months follow-up in 102 patients. 

“Merck is steadfast in its commitment to patients with bladder cancer, including advancing research to meet unmet medical needs. Patients with high-risk NMIBC 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 said Roy Baynes, MD, PhD, senior vice president and head of global clinical development, chief medical officer, Merck Research Laboratories. “We look forward to participating in the advisory committee meeting and to continuing to work with the FDA as they review this supplemental application for KEYTRUDA.”

Fifteen patients experienced recurrence after having a CR. However, no patients progressed to muscle-invasive or metastatic disease.

The safety profile was consistent with previous experiences. Less than 70% of patients (n = 66) experienced treatment-related adverse events (TRAEs). The most common all-grade TRAEs observed were pruritus (10.8%), diarrhea (10.8%), fatigue (9.8%), hypothyroidism (6.9%), and maculopapular rash (5.9%). Thirteen patients also developed grade 3/4 TRAEs. There were also immune-related adverse events seen in 18.6% (n = 19) of patients in the study.

Patients received 200 mg of pembrolizumab intravenously, every 3 weeks, for up to 24 months in the phase II clinical trial. The primary endpoints were CR and disease-free survival rates. The secondary endpoint was DoR.

Patients with histologically-confirmed NMIBC and CBG-unresponsive high-risk non-muscle-invasive bladder cancer after treatment with adequate BCG therapy were eligible to enroll. Patients must have had fully resected disease at study entry, available tissue from a newly obtained core biopsy of a tumor lesion that was not previously irradiated, an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2, and adequate organ function. Participants were also required to be ineligible for radical cystectomy or refusal of radical cystectomy.

Individuals who were excluded for the study were those with muscle-invasive, locally advanced nonresectable, or metastatic urothelial carcinoma, concurrent extra-vesical, evidence of interstitial lung disease or active non-infectious pneumonitis, an active infection requiring systemic therapy, known human immunodeficiency virus, known active Hepatitis B or C infection, active autoimmune disease, or another malignancy that require active therapy. Participants could not enroll if they had prior intervening intravesical chemotherapy or immunotherapy, chemotherapy, targeted small molecule therapy, an allogeneic tissue/solid organ transplant, radiation therapy, or therapy with an anti-programmed cell death 1. Women who were pregnant or breastfeeding were also excluded from the study.

Pembrolizumab, an anti-PD-1 agents, has standing indications for treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who have disease progression during or after platinum-containing chemotherapy and for patients with locally advanced or mUC who are not eligible for cisplatin-containing chemotherapy and whose tumors express PD-L1 [combined positive score ≥10] as determined by an FDA-approved test, or in patients who are not eligible for any platinum-containing chemotherapy regardless of PD-L1 status.

The KEYNOTE-057 study is actively recruiting and plans to conclude in July of 2023. The target action date for the approval of pembrolizumab for the treatment of NMIBC is January 2020.
  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) [press release]. Kenilworth, NJ: Merck; December 2 , 2019. https://bit.ly/34DcG62. 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). Presented at the 2019 ASCO Meeting; May 31–June 4, 2019; Chicago, Illinois. Abstract 350.

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