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

Abstract

Background Fibroblast growth factor receptor ({FGFR}) 2 alterations are implicated in {CCA}. Pemigatinib is a selective, potent, oral {FGFR}1, 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} ({NCT}02924376). Methods Eligible adults had disease progression after ≥1 prior treatment and documented {FGF}/{FGFR} gene status. Pts assigned to cohorts A ({FGFR}2 gene rearrangements/fusions), B (other {FGF}/{FGFR} gene alterations), or C (no {FGF}/{FGFR} gene alterations) received oral pemigatinib 13.5mg {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; 1pt 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 {FGFR}2 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.