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Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma

javle, milind and lowery, maeve and shroff, Rachna and weiss, karl heinz and springfield, Christoph and borad, mitesh and ramanathan, ramesh and goyal, lipika and sadeghi, saeed and maraculla, teresa and el-khoueiry, anthony and kelley, robin kate and borbath, ivan and choo, su pin and oh, Do-Youn and philip, a.philip and chen, li-tzong and reungwetwattana, thanyanan and van cutsem, eric and yeh, kun-huei and ciombor, kristen and zhu, andrew x and abou-alfa, ghassan k and bekaii-saab, tanios and finn, michael (2017) Phase II Study of BGJ398 in Patients With FGFR-Altered Advanced Cholangiocarcinoma. Journal of clinical oncology. ISSN 1527-7755; 0732-183X

Abstract

Abstract
Background: There is no standard treatment for patients with cholangiocarcinoma who fail first line gemcitabine-based therapy. Fibroblast growth factor receptor 2 (FGFR2) fusions/translocations are present in 13% to 17% of intrahepatic cholangiocarcinomas. BGJ398, an orally bioavailable, selective pan-FGFR kinase inhibitor, has shown preliminary clinical activity against tumors with FGFR alterations.
Patients and Methods: A multi-center, open label, phase 2 study evaluated BGJ398 antitumor activity in patients 18 years or older with advanced or metastatic cholangiocarcinoma containing FGFR2 fusions/translocations or other FGFR alterations and progression on prior therapy. Patients received BGJ398 125 mg once daily for 21 days, then 7 days off (28-day cycles). The primary endpoint was investigator-assessed overall response rate.
Results: Sixty-one patients (35 females; median age 57 years) with FGFR2 fusion (n=48), mutation (n=8), or amplification (n=3) participated. At the pre-specified data cutoff (June 30, 2016), 50 patients had discontinued treatment. The overall response rate was 14.8%, disease control rate 75.4%, and estimated median progression-free survival 5.75 months (95% CI: 4.27–7.56 months). All responsive tumors contained FGFR2 fusions. Adverse events included hyperphosphatemia (72.1% all grade; 16.4% grade 3/4), fatigue (36.1%), stomatitis (29.5%), and alopecia (26.2%). Grade 3/4 treatment related adverse events occurred in 25 (41%) patients and included hyperphosphatemia (16.4%), stomatitis (6.6%), and palmar plantar erythrodysesthesia syndrome (4.9%).
Conclusions: BGJ398 is a first-in-class FGFR kinase inhibitor with manageable toxicities that shows meaningful clinical activity against chemotherapy-refractory cholangiocarcinoma containing FGFR2 fusions. This promising antitumor activity supports continued development of BGJ398 in this highly selected patient population.

Item Type: Article
Date Deposited: 16 Jan 2018 00:45
Last Modified: 07 Feb 2018 00:45
URI: https://oak.novartis.com/id/eprint/33502

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