Merck announced a label update for Keytruda, Merck’s anti-PD-1 therapy, for its indication in first-line advanced urothelial carcinoma (bladder cancer) in the US. The US Food and Drug Administration (FDA) have converted this indication from an accelerated to a full (regular) approval. In addition, as part of the label update, this indication has been revised to be for the treatment of patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for any platinum-containing chemotherapy.
Previously, Keytruda was indicated for the treatment of patients with locally advanced or mUC who were not eligible for cisplatin-containing chemotherapy and whose tumors expressed PD-L1 (Combined Positive Score [CPS] =10), as determined by an FDA-approved test, or in patients who were not eligible for any platinum-containing chemotherapy regardless of PD-L1 status. This indication was approved under accelerated approval based on tumor response rate and duration of response. Continued approval was contingent upon verification and description of clinical benefit in confirmatory trials. The subsequent phase 3 trial KEYNOTE-361, evaluating Keytruda as monotherapy and in combination with chemotherapy for the first-line treatment of patients with advanced or mUC who were eligible for platinum-containing chemotherapy, did not meet its pre-specified dual primary endpoints of overall survival or progression-free survival, compared with standard of care chemotherapy.
This label update follows the FDA’s Oncologic Drugs Advisory Committee (ODAC) meetings held earlier this year as part of an industry-wide evaluation of indications based on accelerated approvals that have not met their post-marketing requirements.
“While the treatment landscape has evolved, an unmet need remains for appropriate patients newly diagnosed with certain types of advanced urothelial carcinoma who are not eligible for platinum-containing chemotherapy,” said Dr. Scot Ebbinghaus, vice president, clinical research, Merck Research Laboratories. “We are confident in the role Keytruda will continue to play for these patients who have few other treatment options and are working with urgency to advance studies to help more patients living with bladder and other types of cancer.”
In addition to this first-line indication, Keytruda Is approved for the treatment of patients with locally advanced or mUC who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Keytruda is also approved for the treatment of patients with Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer with carcinoma in situ with or without papillary tumors that are ineligible for or have elected not to undergo cystectomy.
Keytruda is an anti-programmed death receptor-1 (PD-1) therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.