FDA Withdraws Infigratinib Approval for Cholangiocarcinoma

• The FDA approval for infigratinib (Truseltiq) to treat cholangiocarcinoma has been withdrawn.
• The sponsor had trouble finding enough patients for a required confirmatory study and decided it was not commercially viable to keep selling the drug for this use.
• The planned phase 3 trial to see if infigratinib was better than standard treatment was discontinued.

The approval of infigratinib for the treatment of patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma harboring an FGFR2 fusion or other rearrangement has been withdrawn by the FDA.¹

The sponsor of the agent, QED Therapeutics, cited difficulties enrolling patients to the required confirmatory study following infigratinib’s accelerated approval in May 2021 for the treatment of patients with cholangiocarcinoma who harbor an FGFR2 gene fusion or rearrangement.

In addition to determining the continued distribution of infigratinib for the second-line treatment of cholangiocarcinoma to be not commercially reasonable, the sponsor voluntarily requested the withdrawal of infigratinib.

The phase 3 PROOF trial (NCT03773302) sought to assess the safety and efficacy of infigratinib compared with standard-of-care gemcitabine plus cisplatin for the frontline treatment of patients with unresectable, recurrent, or metastatic cholangiocarcinoma harboring FGFR2 gene fusions and translocations.²

Bile duct cancer is a rare disease in which malignant (cancer) cells form in the bile ducts. Bile duct cancer is also called cholangiocarcinoma: © Thipphaphone - stock.adobe.com

The multicenter, open-label, controlled study randomized patients in a 2:1 fashion to receive infigratinib or gemcitabine plus cisplatin. In the experimental arm of the study, patients were being treated with infigratinib at a dose of 125 mg orally daily given 3 weeks on, 1 week off. In the active comparator arm, gemcitabine plus cisplatin was given. Patients who experienced disease progression while receiving the combination of gemcitabine and cisplatin were allowed to cross over and receive infigratinib if certain criteria are met.

Investigators evaluated the primary end point of progression-free survival (PFS). Secondary end points of the study included overall survival, investigator-assessed PFS, overall response rate, best overall response, duration of response, disease control rate, number of patients with an adverse event (AE), and number of patients with a serious AE.

While not closed for safety reasons, the study has been terminated.1 The sponsor decided to close the study due to the discontinuation of infigratinib development in oncology within the sponsor's territory.

REFERENCES:

1. Withdrawn: FDA grants accelerated approval to infigratinib for metastatic cholangiocarcinoma. FDA. May 16, 2024. Accessed May 20, 2024. https://tinyurl.com/yc7kkj4s

2. Phase 3 study of BGJ398 (oral infigratinib) in first line cholangiocarcinoma with FGFR2 gene fusions/​translocations. ClinicalTrials.gov. Updated May 8, 2024. Accessed May 20, 2024. https://clinicaltrials.gov/study/NCT03773302