155O - Efficacy of TAS-120, an irreversible fibroblast growth factor receptor inhibitor (FGFRi), in patients with cholangiocarcinoma and FGFR pathway alterations previously treated with chemotherapy and other FGFRi’s

Abstract

Background: TAS-120, an irreversible FGFR1–4i, has demonstrated preclinical efficacy in tumour models bearing FGFR aberrations. A phase 1 study of TAS-120 (8–24 mg QD) in adult patients (pts) with advanced solid tumours (NCT02052778) found the maximum tolerated dose to be 20 mg QD. Here, we report results from pts with cholangiocarcinoma (CCA) enrolled in this study. Methods: Pts with CCA were enrolled at 16-, 20-, and 24-mg dosing levels and were included in this analysis. FGF/FGFR status was evaluated by local institutions or commercial laboratories. Pts were treated until disease progression or unacceptable toxicity. Results: 45 pts with CCA (intrahepatic n = 41) harbouring FGF/FGFR aberrations were treated at 16 (n = 24), 20 (n = 14), and 24 mg (n = 7) QD (median age 53 y [range 29–73], 76% female, 58% ECOG PS 1, 42% ECOG PS 0). 28 pts (62%) had tumour FGFR2 gene fusions; 17 (38%) had other FGF/FGFR aberrations. All pts received prior systemic therapy; 13 received ≥1 prior reversible FGFRi. Of the 28 pts with FGFR2 gene fusions, 20 (71%) experienced tumour shrinkage and 7 achieved confirmed partial responses (cPRs; 6 remain on treatment, 1 with an ongoing cPR >1 y). The objective response rate was 25%. 15/28 (54%) pts had stable disease as best response; 7 remain on treatment. The disease control rate was 79%. Of the 17 patients with other FGF/FGFR aberrations, 3 had cPRs (all had FGFR2 rearrangements; 1 also had FGFR2 amplification). Median treatment time was 7.4 mo. Of the 13 patients with prior FGFRi treatment, 4 (3 with FGFR2 gene fusions, 1 with FGFR2 amplification) had cPRs. Treatment-related adverse events (TRAEs) of any grade included hyperphosphatemia (78%), increased aspartate aminotransferase (29%), dry skin (29%), diarrhoea (27%), and dry mouth (27%). Grade ≥3 TRAEs were reported in 23/45 (51%) pts; the most common was hyperphosphatemia (22%). Conclusions: TAS-120 demonstrated compelling clinical activity and a manageable AE profile in pts with CCA and FGFR2 gene fusions and showed efficacy in pts with progression on prior FGFRi’s. A phase 2 study has been initiated. Editorial acknowledgement: Editorial assistance was provided by Wendy Sacks of Scientific Connexions (Lyndhurst, NJ, USA). Clinical trial identification: NCT02052778. Legal entity responsible for the study: Taiho Oncology, Inc. and Taiho Pharmaceutical Co., Ltd. Funding: Taiho Oncology, Inc. and Taiho Pharmaceutical Co., Ltd. Disclosure: F. Meric-Bernstam: Grant/research support: Novartis, AstraZeneca, Taiho, Debiopharm. R.K. Kelley: Consulting/advisory: Bayer AG, Debiopharm, Agios, AZ, BMS; Research funding: Eli Lilly, Exelixis, Regeneron, Celgene, Tekmira, Sanofi, Novartis, BMS, MedImmune, Merck Sharp & Dohme, Agios, AZ, Adaptimmune Therapeutics. C. Hierro: Research: Bayer; Travel, accomodation: Roche, Lilly. R. Winkler: Employment: Taiho Oncology, Inc.; Travel, accommodations, expenses: Taiho Oncology, Inc, H. He: Full-time employment: Taiho Oncology. J. Huang: Employment: Taiho Oncology, Inc. L. Goyal: Consulting: Debiopharm. All other authors have declared no conflicts of interest.