AstraZeneca's Imfinzi strikes immunotherapy's first win in bile duct cancer, with Merck's Keytruda behind

The addition of Imfinzi to chemotherapy has helped newly diagnosed patients with advanced biliary tract cancer live longer in a phase 3 trial, AstraZeneca said. (AstraZeneca)

While other cancer immunotherapies are busy expanding into different tumor types, AstraZeneca’s Imfinzi has been a lung cancer story. But the company is now trumpeting a first-of-its-kind win for the drug.

The addition of Imfinzi to chemotherapy has helped newly diagnosed patients with advanced biliary tract cancer live longer, AZ unveiled Monday. The improvement was statistically significant and clinically meaningful, the company said.

The readout came from an interim analysis of the phase 3 Topaz-1 trial and marked the first time an immuno-oncology regimen beat standard of care in a randomized trial for front-line biliary tract cancer, a rare gastrointestinal cancer that reports about 50,000 new diagnoses each year across the U.S., Europe and Japan.

The trial covered patients with cancers that form in the bile ducts—called cholangiocarcinoma—which is more common in China and Thailand, and with gallbladder cancer, which is mainly found in South America, India and Japan. The umbrellas term also includes ampullary carcinoma, but the trial excluded this disease subtype.

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“Patients with advanced biliary tract cancer are in dire need of new treatments as progress in the 1st-line setting has remained largely stagnant for more than 10 years,” said Do-Youn Oh, M.D., Ph.D., from Seoul National University Hospital and principal investigator of the Topaz-1 trial, in a statement.

Last April, the FDA cleared Incyte’s Pemazyre as the first targeted treatment for cholangiocarcinoma. But the drug is meant for patients who have tumors that have an abnormality in the FGFR2 gene and have been previously treated with a standard chemotherapy combo. BridgeBio followed this June with an accelerated approval for Truseltiq in the same setting.

In August, Servier’s Tibsovo branched out into cholangiocarcinoma, but the targeted drug is also limited for previously treated disease bearing an IDH1 mutation.

Although Imfinzi is the first PD-1/L1 inhibitor to succeed in first-line bile duct cancer, it’s not the only one targeting the field. Merck & Co. is running the front-line phase 3 Keynote-966 trial for Keytruda, which started about six months after Imfinzi’s Topaz-1.

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Bile duct cancer marks Imfinzi’s second positive gastrointestinal cancer readout in just a few days, Susan Galbraith, AZ’s oncology R&D chief, noted in a statement. The PD-L1 inhibitor’s pairing with AZ’s investigational CTLA-4 inhibitor tremelimumab topped Bayer’s Nexavar as a first-line treatment for liver cancer in the phase 3 Himalaya trial.

Merck’s Keytruda and Bristol Myers Squibb’s Opdivo have previously both posted failures in liver cancer; Opdivo had to remove an accelerated approval in the second line after a confirmatory trial trip-up in the first-line setting. And Keytruda’s conditional nod in the second line is also hanging in the balance.

Besides bile duct cancer and liver cancer, AZ is also evaluating Imfinzi in other GI cancers, including esophageal and stomach cancers. Beyond the immunotherapy, the company has Daiichi Sankyo-partnered Enhertu and Merck-partnered Lynparza under experiments for various GI cancers.