People with advanced cholangiocarcinoma that has a genetic change called an FGFR2 fusion or an FGFR2 rearrangement have a new treatment option: On September 23, 2026, the U.S. Food and Drug Administration (FDA) approved a targeted therapy called lirafugratinib (Lyrfigtu) for this group of patients. The clinical trial that resulted in the drug’s approval was led by Alison Schram, MD, an early drug development specialist at Memorial Sloan Kettering Cancer Center (MSK).
Cholangiocarcinoma, also known as bile duct cancer, is a cancer that begins in the tubes that carry digestive fluid between the liver and small intestine. Between 10% and 20% of these cancers are driven by FGFR2.
“Cholangiocarcinoma is a rare cancer that is almost always caught after it has spread, making it extremely challenging to treat,” Dr. Schram says. “Any time we find a new treatment for patients with this disease, it can make a meaningful difference to them and their families.”
How does lirafugratinib work?
Lirafugratinib is the latest cancer drug that acts on a family of proteins called FGFR (for fibroblast growth factor receptor). It is different from earlier drugs because it exclusively affects one particular protein in the group, FGFR2. Changes in FGFR2 and other FGFR proteins are detected with tumor tests like MSK-IMPACT®.
The approval of lirafugratinib was based on phase 1/2 clinical trial that treated 116 patients around the world. The study was part of a larger trial, called ReFocus, which is evaluating the effectiveness of lirafugratinib in a variety of tumors with FGFR2 defects.
The study of patients with cholangiocarcinoma found that:
- Almost half of patients (46%) saw their cancer respond to lirafugratinib, meaning that their tumors shrank substantially.
- On average, the drug worked for nearly a year (11.8 months), and most patients did not have their tumors grow during that time.
What are the side effects of lirafugratinib?
Lirafugratinib, which is taken once a day as a pill, does have side effects. The most common ones were:
- Redness and swelling in the hands and feet
- Sores in the mouth
- Changes to the fingernails and toenails
- Dry eyes and mouth
More serious side effects were also seen in some patients. These included:
- A buildup of phosphate in the blood
- More severe eye problems, such as fluid buildup under the retina
Patients taking lirafugratinib will need to be monitored closely for side effects. A full list of those side effects is available here.
What are the next steps for lirafugratinib?
Lirafugratinib is currently only approved for patients with previously treated cholangiocarcinoma.
It is also being studied in other types of solid tumors with FGFR2 fusions and rearrangements. That phase 2 trial is currently open at MSK and other hospitals.
“These kinds of studies, known as basket trials, match patients with drugs based on the mutations found in their tumors, rather than where in the body the tumors originate,” Dr. Schram says. “Basket trials are especially important for rare cancers, where it can be hard to find enough patients to enroll in studies.”
Funding and disclosures
The development of lirafugratinib was funded by Elevar Therapeutics, which makes the drug.
Dr. Schram’s disclosures are available on her webpage.
Key takeaways
- The FDA has approved lirafugratinib, giving patients with advanced cholangiocarcinoma that carries an FGFR2 fusion or rearrangement a new option for targeted therapy.
- Lirafugratinib works by selectively targeting the FGFR2 protein, which drives between 10% and 20% of bile duct cancers.
- In the clinical trial that led to the drug’s approval, nearly half of patients (46%) saw their tumors shrink substantially, and the drug remained effective for an average of nearly a year (11.8 months).
- While lirafugratinib is taken at home as a once-daily pill, patients must be closely monitored for side effects, some of which may be severe.