FDA Accepts sBLA for Pembrolizumab/Chemo in Advanced Biliary Tract Cancer

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The regulatory agency has set a Prescription Drug User Fee Act date of February 7, 2024 for pembrolizumab plus chemotherapy as a treatment for patients with advanced or metastatic biliary tract cancer.

Supporting data for the sBLA came from the phase 3 KEYNOTE-966 trial (NCT04003636), in which investigators assessed the efficacy and safety of pembrolizumab plus chemotherapy vs chemotherapy alone in the treatment of patients with advanced unresectable or metastatic biliary tract cancer.

Supporting data for the sBLA came from the phase 3 KEYNOTE-966 trial (NCT04003636), in which investigators assessed the efficacy and safety of pembrolizumab plus chemotherapy vs chemotherapy alone in the treatment of patients with advanced unresectable or metastatic biliary tract cancer.

The FDA has accepted a supplemental biologics license application (sBLA) for pembrolizumab (Keytruda) plus gemcitabine and cisplatin for the treatment of those with locally advanced unresectable or metastatic biliary tract cancer, according to a press release from Merck.1

The agency has set a Prescription Drug User Fee Act date of February 7, 2024 for pembrolizumab plus chemotherapy in this indication.

“Most biliary tract cancers go undetected until an advanced stage, at which point many patients are ineligible for surgery and have few treatment options,” Scot Ebbinghaus, MD, vice president of Global Clinical Development at Merck Research Laboratories, said in the press release. “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.”

Supporting data for the sBLA came from the phase 3 KEYNOTE-966 trial (NCT04003636), in which investigators assessed the efficacy and safety of pembrolizumab plus chemotherapy vs chemotherapy alone in the treatment of patients with advanced unresectable or metastatic biliary tract cancer.

With a median follow-up of 25.6 months (range, 18.3-38.4), the median overall survival (OS) was 12.7 months (95% CI, 11.5-13.6) with the pembrolizumab-based regimen vs 10.9 months (95% CI, 9.9-11.6) with chemotherapy alone (Hazard ratio, 0.83; 95% CI, 0.72-0.95; P = .0034).2 Additionally, the 1-year and 2-year OS rates in each respective arm were 52% vs 44% and 24.9% vs 18.1%. Investigators reported that OS outcomes were generally consistent across patient subgroups.

“Biliary tract cancer is rising in incidence worldwide, and unfortunately most patients are diagnosed with this devastating type of cancer at an advanced stage, when the 5-year survival rate is less than 5%,” Robin Kate Kelley, MD, professor of Clinical Medicine in the Division of Hematology/Oncology at the University of California, San Francisco, said at the time of the data readout. “This trial shows that adding [pembrolizumab] to chemotherapy holds the potential to extend life for these patients.”

In the randomized, double-blind phase 3 KEYNOTE-966 trial, 1069 patients were randomly assigned to receive 200 mg of pembrolizumab every 3 weeks for up to 2 years plus gemcitabine and cisplatin or matched placebo and the same chemotherapy backbone.

The primary end point was OS. Secondary end points included progression-free survival, objective response rate, duration of response, and safety.

Patients 18 years and older with a histologically confirmed diagnosis of advanced or unresectable biliary tract cancer and measurable disease based on RECIST v1.1 criteria were eligible to enroll on the trial. Additional eligibility criteria included having a life expectancy longer than 3 months, adequate organ function, and providing archival tumor tissue samples.

The safety profile of pembrolizumab in the KEYNOTE-966 trial was consistent with previous reports of the agent. Grade 3/4 treatment-related adverse effects (TRAEs) occurred in 70% of patients receiving the pembrolizumab-based regimen vs 69% of those receiving chemotherapy alone, with TRAEs leading to death in 2% and 1% of patients in each respective group. Moreover, grade 3/4 immune-mediated AEs occurred in 7% and 4% of patients in each group.

Investigators presented these data in a clinical trials plenary session at the American Association for Cancer Research (AACR) 2023 Annual Meeting.

References

  1. FDA accepts application for Merck’s KEYTRUDA® (pembrolizumab) plus chemotherapy as treatment for advanced or unresectable biliary tract cancer. News release. Merck. June 8, 2023. Accessed June 8, 2023. bit.ly/43vnrpr
  2. 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. Merck. April 16, 2023. Accessed June 8, 2023. bit.ly/3N4jWj0
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