TRUSELTIQ is a kinase inhibitor indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.

For Cholangiocarcinoma with FGFR2 fusions or rearrangements...Infigratinib

...Documented FGFR2 gene fusions/translocations...Have an archival tissue sample available with sufficient tumor for central FGFR2 fusion/translocation molecular testing...

Incidence rate and category of dose-limiting toxicities will be tabulated for patients included in the dose escalation portion of the study, to establish the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RPTD)

...cholangiocarcinoma (CCA)...patients, including 83 (77%) with FGFR2 fusions, received infigratinib...Infigratinib is associated with promising anticancer activity and a manageable AE profile in patients with advanced, refractory CCA with an FGFR2 gene fusion or rearrangement.

Patients with advanced/metastatic or inoperable CCA with FGFR2 gene fusions (determined by local or central laboratory) are randomized 2:1 to oral infigratinib once daily for 21 days of a 28-day treatment cycle vs intravenous standard gemcitabine (1000 mg/m2) + cisplatin (25 mg/m2) on days 1 and 8 of a 21-day cycle.

Median PFS with standard second-line chemotherapy was 4.63 months (95% confidence interval [CI] 2.69-7.16) compared with 6.77 months (95% CI 3.94-7.79) for third- and later-line infigratinib....outcomes from second-line chemotherapy in patients with cholangiocarcinoma and FGFR2 fusions were similar to those reported in the literature for all patients with cholangiocarcinoma regardless of genomic status and remain dismal. Infigratinib administered as third- and later-line treatment resulted in a meaningful benefit.

71 pts (62% women; median age 53 years; median 2 prior lines of therapy) with FGFR2 fusions/translocations were included…. Infigratinib-associated toxicity is manageable, and our efficacy findings suggest clinically meaningful activity after chemotherapy in pts with IHC containing FGFR2 fusions. The efficacy of infigratinib in this study supports FGFR2 as a therapeutic target in FGFR2-fusion IHC.

...all three patients with FGFR2-altered (fusion [n = 2] or mutation [n = 1]) cholangiocarcinoma with pre- and post-treatment target lesion assessments had reduced tumor burden (Fig 3)....BGJ398 demonstrated antitumor activity in FGFR1-amplified sqNSCLC, FGFR3-mutant bladder/urothelial cancer, and FGFR2-gene fusion/mutant cholangiocarcinoma, trongly supporting further biologic and clinical investigation.

Median follow-up was 10.6 months (range 1.1–55.9 months)….Centrally reviewed ORR was 23.1% (95% CI 15.6–32.2) including 1 CR and 24 PRs; median DOR was 5.0 months (range 0.9–19.1 months)....Infigratinib is associated with promising anticancer activity and a manageable AE profile in patients with advanced, refractory CCA with an FGFR2 gene fusion or rearrangement.

All responsive tumors contained FGFR2 fusions. The overall response rate was 14.8% (18.8% FGFR2 fusions only), disease control rate was 75.4% (83.3% FGFR2 fusions only), and estimated median progression-free survival was 5.8 months (95% CI, 4.3 to 7.6 months)....BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions.

A multicenter, open-label, phase II study ( ClinicalTrials.gov identifier: NCT02150967) evaluated BGJ398 antitumor activity in patients age ≥ 18 years with advanced or metastatic cholangiocarcinoma...All responsive tumors contained FGFR2 fusions. The overall response rate was 14.8% (18.8% FGFR2 fusions only), disease control rate was 75.4% (83.3% FGFR2 fusions only), and estimated median progression-free survival was 5.8 months (95% CI, 4.3 to 7.6 months).

Outcomes from second-line chemotherapy in patients with CCA and FGFR2 fusions were similar to those reported in the literature for all patients with CCA regardless of genomic status and remain dismal. Infigratinib administered as third and later-line treatment resulted in a meaningful PFS and ORR benefit in patients with CCA and FGFR2 fusions.

Clinically, in an open-label phase II trial, infigratinib demonstrated a confirmed overall response rate (cORR) of 39.3% in FGFR2 fusion-positive cholangiocarcinoma patients who received infigratinib as second-line therapy (Figure 7). Additionally, clinical benefit was observed in...solid tumors tested positive for FGFR fusions.

Infigratinib has also demonstrated efficacy in FGFR fusion+ PDX models of cholangiocarcinoma, breast cancer, liver cancer, gastric cancer and glioma.