javle, milind, lowery, maeve, shroff, Rachna, weiss, karl heinz, springfield, Christoph, borad, mitesh, ramanathan, ramesh, goyal, lipika, sadeghi, saeed, maraculla, teresa, el-khoueiry, anthony, kelley, robin kate, borbath, ivan, choo, su pin, oh, Do-Youn, philip, a.philip, chen, li-tzong, reungwetwattana, thanyanan, van cutsem, eric, yeh, kun-huei, ciombor, kristen, zhu, andrew x, abou-alfa, ghassan k, 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