The Food and Drug Administration (FDA) has accepted for review the supplemental Biologics License Application (sBLA) for pembrolizumab (Keytruda®) in combination with standard of care chemotherapy (gemcitabine and cisplatin) for the treatment of patients with locally advanced unresectable or metastatic biliary tract cancer.
The sBLA is supported by data from the KEYNOTE-966 trial (ClinicalTrials.gov Identifier: NCT04003636), which compared pembrolizumab, an anti-programmed death receptor-1 (PD-1) therapy, plus gemcitabine/cisplatin (n=533) to placebo plus gemcitabine/cisplatin (n=536) in patients with advanced and/or unresectable biliary tract carcinoma. The primary endpoint was overall survival (OS); secondary endpoints included progression free survival (PFS), objective response rate (ORR), and duration of response (DOR).
Findings showed that after a median follow-up of 25.6 months, pembrolizumab plus chemotherapy reduced the risk of death by 17% (hazard ratio, 0.83 [95% CI, 0.72-0.95]; P =.0034) compared with chemotherapy alone; median OS was 12.7 months for the pembrolizumab arm and 10.9 months for the chemotherapy alone arm. The 1-year and 2-year OS rates were reported to be 52% and 24.9% with pembrolizumab, respectively, vs 44% and 18.1% with chemotherapy alone.
At the final analysis, median DOR was 8.3 months for pembrolizumab and 6.8 months for chemotherapy alone. The difference in PFS and ORR did not reach statistical significance. Median PFS was 6.5 months with pembrolizumab and 5.6 months with chemotherapy alone. For patients receiving pembrolizumab, the ORR was 29% (complete response 2%, partial response 27%); in the chemotherapy alone group, the ORR was 29% (complete response 1%, partial response 27%). No new safety signals were reported in the trial.
“Most biliary tract cancers go undetected until an advanced stage, at which point many patients are ineligible for surgery and have few treatment options,” said Dr Scot Ebbinghaus, vice president, global clinical development, Merck Research Laboratories. “We look forward to working with the FDA to bring a new option to patients with advanced or unresectable biliary tract cancer that may help them live longer.”
A regulatory decision is expected on February 7, 2024.
- FDA accepts application for Merck’s Keutruda® (pembrolizumab) plus chemotherapy as treatment for advanced or unresectable biliary tract cancer. News release. June 8, 2023. https://www.businesswire.com/news/home/20230608005213/en/FDA-Accepts-Application-for-Merck%E2%80%99s-KEYTRUDA%C2%AE-pembrolizumab-Plus-Chemotherapy-as-Treatment-for-Advanced-or-Unresectable-Biliary-Tract-Cancer.
- Merck’s Keytruda® (pembrolizumab) plus chemotherapy significantly improved overall survival compared to chemotherapy alone in patients with advanced or unresectable biliary tract cancer. News release. April 16, 2023. https://www.merck.com/news/mercks-keytruda-pembrolizumab-plus-chemotherapy-significantly-improved-overall-survival-compared-to-chemotherapy-alone-in-patients-with-advanced-or-unresectable-biliary-tract-cancer/.