2550 - FIGHT-202: a phase 2 study of pemigatinib in patients (pts) with previously treated locally advanced or metastatic cholangiocarcinoma (CCA)

Background

Fibroblast growth factor receptor (FGFR) 2 alterations are implicated in CCA. Pemigatinib is a selective, potent, oral FGFR1, 2, and 3 inhibitor. We present data from a phase II, open label, single arm study of pemigatinib in pts with previously treated locally advanced or metastatic CCA (NCT02924376).

Methods

Eligible adults had disease progression after ≥1 prior treatment and documented FGF/FGFR gene status. Pts assigned to cohorts A (FGFR2 gene rearrangements/fusions), B (other FGF/FGFR gene alterations), or C (no FGF/FGFR gene alterations) received oral pemigatinib 13.5 mg QD (21-day cycle; 2 weeks on, 1 week off) until disease progression/unacceptable toxicity. Primary endpoint was centrally confirmed objective response rate (ORR; cohort A); secondary endpoints were ORR (cohorts B, A+B, and C); duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

Results

At data cutoff (Mar 22, 2019), 146 pts were enrolled (cohort A, n = 107; B, n = 20; C, n = 18; 1 pt undetermined). Median (range) age was 59 (26–78) years; 61% and 39% had 1 and ≥2 prior therapies, respectively. Fewer pts discontinued therapy in cohort A (71%) vs B and C (each 100%), mainly for progressive disease (53%, 75%, and 67%, respectively). ORR in cohort A was 35.5% (95% CI, 26.5%–45.4%), with 3 complete responses; median (m) DOR was 7.5 (95% CI, 5.7–14.5) months (mo), DCR was 82% (95% CI, 74%–89%), mPFS and mOS were 6.9 (95% CI, 6.2–9.6) and 21.1 (14.8–not reached) mo (OS not mature at cutoff). In cohorts B and C, no patient achieved a response. Overall, most common adverse events (AEs) were hyperphosphatemia (60%; grade ≥3, 0%), alopecia (49%; 0%), diarrhea (47%; 3%), fatigue (42%; 5%), nail toxicities (42%; 2%), and dysgeusia (40%; 0%). Hyperphosphatemia was managed with diet modifications, phosphate binders, if needed; diuretics or dose reductions/interruptions. Discontinuation, dose reduction and interruption due to AEs occurred in 9%, 14% and 42% of patients, respectively.

Conclusions

These data support pemigatinib as a potential treatment option for previously treated pts with CCA harboring FGFR2 gene rearrangements/fusions.

Clinical trial identification

EudraCT: 2016-002422-36.

Editorial acknowledgement

Editorial assistance was provided by Envision Pharma Group (Philadelphia, PA) and funded by Incyte Corporation.

Legal entity responsible for the study

Incyte Corporation.

Funding

Incyte Corporation.

Disclosure

A. Vogel: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Incyte; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Medac; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Delcath; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Shire. V. Sahai: Research grant / Funding (institution): Agios; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Clovis; Research grant / Funding (institution): Debiopharm; Research grant / Funding (institution): Fibrogen; Advisory / Consultancy, Research grant / Funding (institution): Incyte; Advisory / Consultancy, Research grant / Funding (institution): Ipsen; Research grant / Funding (institution): Merck; Research grant / Funding (institution): NCI; Research grant / Funding (institution): Rafael; Advisory / Consultancy: Halozyme; Advisory / Consultancy: QED; Advisory / Consultancy: NewLink Genetics. A. Hollebecque: Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Amgen; Advisory / Consultancy: Spectrum Pharmaceuticals; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy, Travel / Accommodation / Expenses: Debiopharm; Travel / Accommodation / Expenses: Servier; Travel / Accommodation / Expenses: Incyte; Non-remunerated activity/ies: Bayer; Non-remunerated activity/ies: EISAI; Research grant / Funding (institution): Astrazeneca; Research grant / Funding (institution): BMS; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Janssen Cilag; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Roche; Research grant / Funding (institution): Sanofi. D. Melisi: Advisory / Consultancy, Research grant / Funding (institution): Shire; Advisory / Consultancy, Research grant / Funding (institution): Incyte; Advisory / Consultancy, Research grant / Funding (institution): Evotec; Research grant / Funding (institution): Celgene; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Baxter. R. Al-Rajabi: Research grant / Funding (institution): Incyte. A.S. Paulson: Advisory / Consultancy: AAA; Advisory / Consultancy, Research grant / Funding (institution): Taiho; Advisory / Consultancy: Ipsen; Advisory / Consultancy, Research grant / Funding (institution): BMS; Advisory / Consultancy: Eisai; Advisory / Consultancy: Amgen; Shareholder / Stockholder / Stock options: Aptose; Shareholder / Stockholder / Stock options: Seattle Genetics; Shareholder / Stockholder / Stock options: Immunomedics; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Exelixis. M.J. Borad: Research grant / Funding (institution): Senhwa Pharmaceuticals, Adaptimmune, Agios Pharmaceuticals, Halozyme Pharmaceuticals, Celgene Pharmaceuticals, EMD Merck Serono, Toray, Dicerna, Taiho Pharmaceuticals, Sun Biopharma, Isis Pharmaceuticals, Redhill Pharmaceuticals, Boston Biomed, Basilea, I; Honoraria (self): Exelixis, G1 Therapeutics, Immunonative Therapies, Western Oncolytics, Lynx Group, Inspyr Therapeutics, ADC Therapeutics; Shareholder / Stockholder / Stock options: OncBioMune Pharmaceuticals, Intercept, AVEO; Travel / Accommodation / Expenses: AstraZeneca. A.G. Murphy: Research grant / Funding (institution): BMS. D. Oh: Research grant / Funding (institution): Array; Research grant / Funding (institution): Eli Lilly; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Merck Serono; Advisory / Consultancy: Bayer; Advisory / Consultancy: Taiho; Advisory / Consultancy: ASLAN; Advisory / Consultancy: Halozyme; Advisory / Consultancy: Zymeworks. E. Dotan: Honoraria (self): Boston Medical; Honoraria (self): Armo; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Lilly. D.V. Catenacci: Honoraria (self), Advisory / Consultancy: Merck; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Five Prime; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Taiho; Honoraria (self), Advisory / Consultancy: Lilly; Honoraria (self), Advisory / Consultancy: Genentech/Roche; Honoraria (self), Advisory / Consultancy: Gritstone; Honoraria (self), Advisory / Consultancy: Foundation Medicine; Honoraria (self), Advisory / Consultancy: Tempus; Honoraria (self), Advisory / Consultancy: Guardant Health. E. Van Cutsem: Advisory / Consultancy: Astellas; Advisory / Consultancy: Astrazeneca; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Celgene; Advisory / Consultancy: Incyte; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Advisory / Consultancy, Research grant / Funding (institution): Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (institution): Merck KGaA; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche; Advisory / Consultancy, Research grant / Funding (institution): Servier; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Ipsen. C.F. Lihou: Shareholder / Stockholder / Stock options, Full / Part-time employment: Incyte Corporation. H. Zhen: Shareholder / Stockholder / Stock options, Full / Part-time employment: Incyte Corporation. L. Féliz: Shareholder / Stockholder / Stock options, Full / Part-time employment: Incyte Corporation. G.K. Abou-Alfa: Research grant / Funding (institution): ActaBiologica, Agios, Array, AstraZeneca, Bayer, Beigene, BMS, Casi, Celgene, Exelixis, Genentech, Halozyme, Incyte, Lilly, Mabvax, Novartis, OncoQuest, Polaris Puma, QED, Roche; Advisory / Consultancy: 3DMedcare, Agios, Alignmed, Amgen, Antengene, Aptus, Aslan, Astellas, AstraZeneca, Bayer, Beigene, Bioline, BMS, Boston Scientifc, Bridgebio, Carsgen, Celgene, Casi, Cipla, CytomX, Daiichi, Debio, Delcath, Eisai, Exelixis, Genoscience, Halozyme, Hengrui. All other authors have declared no conflicts of interest.