Tovecimig (CTX-009)

Biliary tract cancer is an adenocarcinoma arising from the epithelium of the biliary tree and comprises intrahepatic cholangiocarcinoma, extrahepatic (perihilar and distal) cholangiocarcinoma, gallbladder cancer, and carcinoma of the ampulla of Vater. Cholangiocarcinoma is subdivided anatomically: intrahepatic cholangiocarcinoma arises above the second-order bile ducts, and the insertion of the cystic duct separates perihilar from distal cholangiocarcinoma. In the United States, perihilar disease accounts for approximately 50% to 60% of cholangiocarcinomas, distal disease for 20% to 30%, and intrahepatic disease for 10% to 20%. Biliary tract cancers account for less than 1% of all cancers worldwide.

Second-line advanced biliary tract cancer is the disease state of participants with locally advanced or metastatic biliary tract cancer whose disease has progressed after first-line systemic therapy, historically cisplatin and gemcitabine and now cisplatin, gemcitabine, and an anti-PD-L1 or anti-PD-1 antibody. In the ABC-06 randomized trial, the primary tumour sites among 162 participants enrolled after progression on cisplatin and gemcitabine were intrahepatic cholangiocarcinoma (72 of 162, 44%), extrahepatic cholangiocarcinoma (45, 28%), gallbladder (34, 21%), and ampullary cancer (11, 7%).

Most risk factors share chronic inflammation of the biliary epithelium and bile stasis. Reported associations include choledochal cyst, Caroli disease, primary sclerosing cholangitis, choledocholithiasis and cholelithiasis, cirrhosis, chronic hepatitis B and C, inflammatory bowel disease, chronic pancreatitis, type 2 diabetes, non-alcoholic fatty liver disease, and, in endemic regions of Southeast Asia, infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis. In most countries the majority of cases remain sporadic with no identifiable risk factor.