Health Canada Approves KEYTRUDA® for Advanced Biliary Tract Carcinoma

Merck, known as MSD outside the U.S. and Canada, revealed that Health Canada has approved the use of KEYTRUDA® (pembrolizumab), Merck's anti-PD-1 therapy, in conjunction with gemcitabine-based chemotherapy. This new approval is intended for adult patients suffering from locally advanced unresectable or metastatic biliary tract carcinoma (BTC). The decision is informed by results from the Phase 3 KEYNOTE-966 trial, which showed significant improvements in overall survival (OS) when compared to chemotherapy alone.

"Biliary tract cancer is often diagnosed in its advanced stages, where survival rates are dismally low," remarked André Galarneau, Executive Director & Vice President, Oncology Business Unit at Merck Canada. "The addition of this new treatment option provides promising survival outcomes, thereby offering more hope for patients battling this aggressive form of cancer."

The KEYNOTE-966 trial was a multicenter, randomized, double-blind, placebo-controlled study (ClinicalTrials.gov NCT04003636). It evaluated the effects of pembrolizumab combined with gemcitabine and cisplatin against a placebo plus gemcitabine and cisplatin for the initial treatment of advanced or unresectable BTC. The primary focus of the trial was overall survival (OS), with secondary endpoints including progression-free survival (PFS) and objective response rate (ORR) as assessed by BICR using RECIST v1.1 criteria.

A total of 1,069 patients with locally advanced unresectable or metastatic BTC were enrolled. These patients had not received prior systemic therapy for their advanced disease. They were randomized in a 1:1 ratio to receive either pembrolizumab (200 mg every three weeks for up to approximately two years) plus gemcitabine and cisplatin, or a placebo plus gemcitabine and cisplatin. Treatment continued until unacceptable toxicity or disease progression. Pembrolizumab could be given for a maximum of 35 cycles (approximately 24 months). Cisplatin was capped at 8 cycles, whereas gemcitabine could continue beyond 8 cycles.

The results revealed that the pembrolizumab with gemcitabine/cisplatin arm had a meaningful and statistically significant improvement in OS compared to the placebo with gemcitabine/cisplatin arm. There was a 17% reduction in the risk of death for the pembrolizumab group (HR=0.83 [95% CI, 0.72-0.95]; p=0.0034) compared to chemotherapy alone. The median PFS was 6.5 months for the pembrolizumab plus chemotherapy group versus 5.6 months for the placebo plus chemotherapy group. The objective response rate at the interim analysis was 28.7% for the pembrolizumab group versus 28.5% for the placebo group.

Common treatment-related side effects (reported in at least 20% of patients) were decreased neutrophil count, anemia, decreased platelet count, nausea, fatigue, and decreased white blood cell count.

Biliary tract cancer encompasses a group of rare, highly aggressive cancers in the gallbladder and bile ducts. It is the second most common type of primary liver cancer after hepatocellular carcinoma, contributing to 15% of liver cancer cases globally. Approximately 211,000 new cases and 174,000 deaths from BTC are reported annually worldwide. The disease is most often diagnosed in individuals aged 50 to 70, and 60-70% of patients are diagnosed at an advanced stage. The prognosis remains poor, with a five-year survival rate of 5% to 15%.

KEYTRUDA® is an anti-programmed death receptor-1 (PD-1) therapy that enhances the immune system's capability to detect and combat tumor cells. It is a humanized monoclonal antibody that inhibits the interaction between PD-1 and its ligands, thereby activating T lymphocytes, which can influence both tumor and healthy cells. Initially approved in Canada in 2015, KEYTRUDA® is indicated for several diseases, including advanced renal cell carcinoma, bladder cancer, non-small cell lung carcinoma, among others.

Merck, known as MSD internationally, harnesses cutting-edge science to save and improve lives globally. For over 130 years, Merck has been dedicated to developing crucial medicines and vaccines, aiming to be the leading research-intensive biopharmaceutical company. The company promotes a diverse and inclusive workforce, operating responsibly to ensure a sustainable, healthy future for all communities.