Phase III Trial Begins for Frontline Pemigatinib in FGFR2+ Cholangiocarcinoma

Steven Stein, MD

Steven Stein, MD

A phase III trial has begun for the investigational agent pemigatinib (INCB54828) in comparison with gemcitabine and cisplatin chemotherapy for the treatment of newly diagnosed patients with metastatic or surgically unresectable cholangiocarcinoma who have activatingFGFR2rearrangements. The first patient has already been treated with the selective FGFR inhibitor in the open-label, randomized FIGHT-302 trial (NCT03656536), according to a press release from Incyte, the company developing the agent.

“We are pleased to initiate FIGHT-302—the first phase III study of pemigatinib—which we hope will add to the growing body of evidence demonstrating its potential as a safe and effective treatment for patients with cholangiocarcinoma with known FGFR2 rearrangements, a rare and potentially life-threatening form of cancer,” Steven Stein, MD, the chief medical officer of Incyte, said in a statement.

FGFR2fusions are considered to be a driver of the disease that occurs almost exclusively in patients with intrahepatic cholangiocarcinoma. Many patients with cholangiocarcinoma have a poor prognosis and are often diagnosed at an older age.

“Most patients that present with cholangiocarcinoma, like those patients to be enrolled in the FIGHT-302 study, have an advanced form of the disease that cannot be surgically removed, and the majority do not respond to the current standard of care, demonstrating the significant need for new treatment options,” Stein added.

The FIGHT-302 trial is planning to enroll about 432 adult patients with cholangiocarcinoma to test the safety and efficacy of pemigatinib. Patients who are randomized to receive the investigational FGFR inhibitor will receive continuous daily, oral therapy of 13.5 mg pemigatinib, whereas patients in the chemotherapy arm will receive 1000 mg/m²of gemcitabine plus 25 mg/m²of cisplatin, both given intravenously on days 1 and 8 of every 3-week cycle for up to 8 cycles. Patients in the control arm who progress on treatment or during the follow-up period will be eligible to cross over to receive pemigatinib.

Patients with known central nervous system metastases, Child-Pugh B or C score, or additional malignancies are ineligible for this trial.

The primary endpoint of the FIGHT-302 study is progression-free survival, and secondary endpoints include overall response rate, overall survival, duration of response, disease control rate, adverse events, and quality of life.

Pemigatinib is also being explored in other solid and hematologic malignancies across several clinical trials, including the FIGHT-207 for previously treated patients with locally advanced, metastatic, or surgically unresectable solid tumors that have activatingFGFRmutations or translocations, irrespective of the tumor type. The agent also previously received a breakthrough therapy designation from the FDA for the treatment of patients with cholangiocarcinoma in the second-line setting.

Reference:

Incyte Announces First Patient Treated in Phase 3 Clinical Trial of Pemigatinib as a First-Line Therapy for Cholangiocarcinoma [press release]. Wilmington, DE: Incyte; June 4, 2019. https://bit.ly/2wxPlTW. Accessed June 4, 2019.