【标准治疗方案】FDA加速批准Infigratinib用于治疗FGFR2+胆管癌

Cholangiocarcinoma refers to a malignant tumor originating from the extrahepatic bile duct. It mostly occurs in men aged 50-70 years old. Common symptoms include abdominal pain, nausea, epigastric mass, fever, etc., and the prognosis is poor. Infigratinib is an oral FGFR tyrosine kinase inhibitor that can selectively bind to FGFR and inhibit FGFR activity, inhibit tumor angiogenesis and tumor cell proliferation, and then induce tumor cell death.

According to BridgeBio, its infigratinib (Truseltiq) has received accelerated approval from the FDA for the treatment of patients with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma carrying FGFR2 fusions. The approval is based on a multicenter, open-label, single-arm Phase 2 trial of CBGJ398X2204 (NCT02150967), in which 108 patients received 125 mg once daily on days 1-21. mg infigratinib is administered, with a 28-day course of treatment.

The median age of the subjects was 53 years (range: 23-81 years), 62.0% of the patients were female, and 57.4% had an ECOG performance status of 1; most patients (99.1%) had stage 4 disease; 68.5% of the patients had lung metastases, 57.4% of the patients had lymph node metastases, and 38.0% of the patients had metastases to other sites. In addition, the median number of prior treatments received by patients was 2; 46.3% of patients had received 1 prior treatment, 29.6% had received 2 treatments, 13.0% had received 3 treatments, and 11.1% had received 4 or more treatments.

The co-primary endpoints of the trial are objective response rate (ORR) and duration of response (DOR), and key secondary endpoints include progression-free survival (PFS), disease control rate (DCR), best ORR, overall survival (OS), and safety.

Researchers presented trial data at the 2021 Gastrointestinal Cancer Symposium. Investigator-assessed ORR was 30.6%; median DOR was 6.0 months. The ORR assessed by the independent review committee was 23.1%, including 1 complete response and 24 partial responses. In addition, 66 patients achieved stable disease and 11 patients experienced disease progression; the median DOR was 5.0 months.

In addition, among patients who had previously received 1 type of treatment, the ORR was 34.0%, the best ORR was 42.0%, and the DCR was 88.0%; among patients who had previously received 2 or more types of treatment, the ORR was 13.8%, the best ORR was 27.6%, and the DCR was 81.0%.

"The results of this trial are an important milestone for patients with cholangiocarcinoma who carry FGFR2 fusions," said Susan, chief medical officer of QED Therapeutics, a subsidiary of BridgeBio. Dr. Moran said at a press conference. "Based on the currently observed efficacy, our research team believes that infigratinib has a better prospect in some FGFR2-driven diseases, and we will further evaluate its safety and efficacy in this field."

In terms of safety, most adverse events (AEs) that occurred were grade 1 or 2, and most were controllable and reversible. The most common AEs included calcium phosphate homeostasis (85.2%), tissue calcification (2.8%), pathological fracture (0.9%), vascular calcification/mineralization (0.9%), and eye disease (70.4%). In addition, the incidence of central serous retinopathy/retinal pigment epithelial detachment events was 16.7%.

"Although new targeted therapies have extended survival for many cancer patients, treatment options for cholangiocarcinoma are extremely limited and survival data are low," said Milind, MD, MD Anderson Cancer Center, University of Texas Dr. Javle said at a press conference. "In this study, infigratinib demonstrated good efficacy and was well tolerated in terms of safety when used to treat cholangiocarcinoma harboring FGFR2 fusions, and is expected to become a standard treatment option for this patient population."

Reference: https://www.cancernetwork.com/view/infigratinib-granted-accelerated-approval-for-fgfr2-cholangiocarcinoma