2954 - Interim results of fight-202, a phase 2, open-label, multicenter study of INCB054828 in patients (pts) with previously treated advanced/metastatic or surgically unresectable cholangiocarcinoma (CCA) with/without fibroblast growth factor (FGF)/FGF receptor (FGFR) genetic alterations

Background

Dysregulation of FGFR signaling by FGFR translocations is involved in the pathogenesis of CCA. FGFR2 translocations occur almost exclusively in pts with intrahepatic CCA (iCCA) with an incidence of 13%–15%.¹ INCB054828, a selective, potent oral inhibitor of FGFR1, 2, and 3, is being evaluated in a phase 2 study (NCT02924376) of pts with previously treated CCA.

Methods

Pts are enrolled into cohort A (FGFR2 translocations), cohort B (other FGF/FGFR genetic alterations [GA]), or cohort C (no FGF/FGFR GAs) and receive oral INCB054828 13.5 mg once daily on a 21‐day cycle (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary endpoint is objective response rate (ORR) per RECIST v1.1 in cohort A based on independent review. Secondary endpoints include ORR in cohorts B and C, progression-free survival (PFS), overall survival, and safety. We report interim efficacy and safety data.

Results

At data cutoff (27 Nov 2017) 47, 22, and 18 pts were enrolled in cohorts A, B, and C, respectively. In cohort A, 94% (44/47) had iCCA, 98% (46/47) had ECOG PS ≤ 1, and 60% (28/47) received ≥ 2 prior therapies. Of 45 evaluable pts in cohort A, 8 (18%) had a confirmed partial response (PR; 1/8 with unconfirmed complete response) and 26 (58%) had stable disease (3/26 had unconfirmed PRs); the best ORR was 24% (95% CI, 12%–37%). Median PFS was 6.8 months (95% CI, 3.6–9.2 months). No responses were observed in cohorts B or C; median PFS was 1.4 and 1.5 months, respectively. The most common treatment-emergent adverse events (TEAEs) in all pts (N = 87) were hyperphosphatemia (56%), alopecia (36%), and diarrhea (32%). Hyperphosphatemia was managed with diet, phosphate binders, or dose modification. Most frequent grade 3/4 TEAEs were hyponatremia (8%) and hypophosphatemia (7%).

Conclusions

INCB054828 was generally well tolerated and showed preliminary efficacy in pts with previously treated advanced iCCA with FGFR2 translocations. Long-term follow-up data will be presented. 1. Graham RP, et al. Hum Pathol. 2014;45:1630-1638.

Clinical trial identification

NCT02924376.

Legal entity responsible for the study

Incyte Corporation.

Funding

Incyte Corporation.

Editorial Acknowledgement

Medical writing assistance was provided by Michael R. Convente, PhD, of Scientific Pathways, Inc, and funded by Incyte.

Disclosure

A. Hollebecque: Honoraria: Servier, Merck, Serono; Membership on any entity’s Board of directors, advisory committees: Amgen, Gritstone Oncology. M. Borad: Research funding: Incyte Pharmaceuticals. V. Sahai: Consultancy, Honoraria: Halozyme, Celgene, NewLink; Research funding: Bristol-Myers Squibb, Celgene; Membership on any entity\'s Board of directors, Advisory committees: Celgene, Halozyme. D.V.T. Catenacci: Consultancy (Includes expert testimony): Merck, Bristol-Myers Squibb, Lilly, Five Prime, Genentech/Roche, Amgen, Taiho, Foundation Medicine, Guardant Health; Research funding: Genentech/Roche; Honoraria: Merck, Bristol-Myers Squibb, Lilly, Five Prime, Genentech/Roche, Amgen, Taiho, Foundation Medicine, Guardant Health; Speakers Bureau: Foundation Medicine, Guardant Health, Lilly, Merck, Genentech. A. Murphy: Research funding: Bristol-Myers Squibb. G. Vaccaro: Consultancy (Includes expert testimony): Exelixis; Research funding: Celgene, Merck Sharpe, Dohme, Lilly, Astellas, EMD Serono, Incyte, Bristol-Myers Squibb, Array BioPharma, Newlink Genetics; Honoraria: Bayer. A. Paulson: Equity Ownership: Immunomedics; Membership on any entity’s Board of directors, Advisory committees: Ipsen, Bristol-Myers Squibb, Eisai, Taiho, Merrimack. D-Y. Oh: Research funding: AstraZeneca. L. Féliz, C. Lihou, H. Zhen: Employee, Equity ownership: Incyte. G.K. Abou-Alfa: Consultancy (Includes expert testimony): Agios, Amgen, Antengene, Aptus, Aslan, Astellas, AstraZeneca, Bayer, Bristol-Myers Squibb, Boston Scientific, Carsgen, Celgene, Casi, CytomX, Daiichi, Debio, Delcath, Eisai, Exelixis, Gilead, Halozyme, Inovio, Ipsen, Merck, Onxeo, PCI Biotech, Roche, Sanofi, Servier, Silenseed, Sillajen, Sirtex, Vicus, Yakult; Research funding: Agios, Array, AstraZeneca, Bayer, Bristol-Myers Squibb, Casi, Celgene, Exelixis, Genentech, Incyte, Lilly, Mabvax, Medimmune, Momenta, Novartis, OncoMed Pharmaceuticals, Roche.