TY - JOUR
T1 - Pemigatinib for previously treated, locally advanced or metastatic cholangiocarcinoma
T2 - a multicentre, open-label, phase 2 study
AU - Abou-Alfa, Ghassan K.
AU - Sahai, Vaibhav
AU - Hollebecque, Antoine
AU - Vaccaro, Gina
AU - Melisi, Davide
AU - Al-Rajabi, Raed
AU - Paulson, Andrew S.
AU - Borad, Mitesh J.
AU - Gallinson, David
AU - Murphy, Adrian G.
AU - Oh, Do Youn
AU - Dotan, Efrat
AU - Catenacci, Daniel V.
AU - Van Cutsem, Eric
AU - Ji, Tao
AU - Lihou, Christine F.
AU - Zhen, Huiling
AU - Féliz, Luis
AU - Vogel, Arndt
N1 - Funding Information:
This study was funded by Incyte Corporation (Wilmington, DE, USA). We thank the study participants and the investigators and research teams who contributed to the study. We also thank Ian M Silverman and Timothy C Burn (Incyte Research Institute, Wilmington, DE, USA) for contributing data from FGF/FGFR genomic analyses and Swamy Yeleswaram (Incyte Research Institute) for contributing to population pharmacokinetic analyses. Medical writing assistance was provided by Simon J Slater (Envision Pharma Group, Philadelphia, PA, USA), funded by Incyte Corporation.
Funding Information:
GKA-A reports research grants and personal fees for consulting from Incyte Corporation, both related and unrelated to the present work; research grants and personal fees for consulting from Agios, AstraZeneca, Bayer, Beigene, Bristol-Myers Squibb, Celgene, Exelixis, Polaris, and QED, unrelated to the present work; research grants from Array, ActaBiologica, Genentech, CASI, Mabvax, Halozyme, Novartis, OncoQuest, Puma Biotechnology, and Roche, unrelated to the present work; and personal fees for consulting from Autem, Berry Gemomics, Bioline, CytomX, Debiopharm, Eisai, Eli Lilly, Flatiron, Genoscience, Ipsen, Jansen, LAM, Loxo, Merck, MINA, Pfizer, RedHill, Silenseed, Sillajen, Sobi, Targovax, Therabionics, Twoxar, and Yiviva, unrelated to the present work. VS reports institutional research grants from Incyte Corporation, both related and unrelated to the present work; institutional research grants from Agios, Bristol-Myers Squibb, Celgene, Clovis, Debiopharm, Fibrogen, Medimmune, Merck, NCI, and Rafael, unrelated to the present work; institutional research grants and honoraria from Halozyme, and Ipsen, unrelated to the present work; and personal fees for consulting from QED, Klus, and NewLink Genetics, unrelated to the present work. AH reports research grants from Incyte Corporation, both related and unrelated to the present work; personal fees for consulting from Amgen, Spectrum Pharmaceuticals, Eli Lilly, Debiopharm, Servier, Bayer, and Eisai, unrelated to the present work; research grants from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen Cilag, Merck, Novartis, Pfizer, Sanofi, and Roche, unrelated to the present work. GV reports personal fees for consulting from Bayer, Genentech, Exelixis, Incyte Corporation, Alexion, Amgen, Novartis, Celgene, and Astellas, unrelated to the present work; and institutional research grants from Astellas, Eli Lilly, Merck, Incyte Corporation, EMD Serono, Celgene, ER Squibb and Sons, and Boston Scientific, unrelated to the present work. DM reports research grants and personal fees for consulting from Incyte Corporation, both related and unrelated to the present study; research grants and personal fees for consulting from Shire, Evotec, and iOnctura, unrelated to the present work; research grants from Celgene, unrelated to the present work; and personal fees for consulting from Eli Lilly and Baxter, unrelated to the present work. RA-R reports research grants from Incyte Corporation, related to the present work; equity in Seattle Genetics, unrelated to the present work; equity stake in Actinium Pharmaceutical, unrelated to the present work; and personal fees for consulting from Sirtex, unrelated to the present work. ASP reports research grants from Incyte Corporation, both related and unrelated to the present work; personal fees from AAA, Ipsen, Eisai, and Amgen, unrelated to the present work; grants and personal fees from Taiho and Bristol-Myers Squibb, unrelated to the present work; research grants from Bayer and Exelixis, unrelated to the present work; and stock ownership in Aptose, Seattle Genetics, Immunomedics, Actinium, and Alexion, unrelated to the present work. MJB reports research grants from Incyte Corporation, both related and unrelated to the present work; research grants from Senhwa, Adaptimmune, Agios, Halozyme, Celgene, EMD Serono, Toray, Dicerna, Taiho, Sun BioPharma, Isis Pharmaceuticals, RedHill, Boston Biomedical, Basilea, miRNA Therapeutics, Medimmune, Bioline, Sillajen, ARIAD, Puma Biotechnology, Novartis, and QED, unrelated to the present work; institutional funding from Pieris, unrelated to the present work; shares, stock ownership, and stock options in OncBioMune Pharmaceuticals, Intercept, and AVEO, unrelated to the present work; and personal fees for consulting from Exelixis, G1 Therapeutics, Immunovative Therapies, Western Oncolytics, Lynx Group, AstraZeneca, Inspyr Therapeutics, ADC Therapeutics, and Merck, unrelated to the present work. AGM reports research grants from Bristol-Myers Squibb, unrelated to the present work. D-YO reports personal fees for consulting from Genentech–Roche, Novartis, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, and Zymeworks, unrelated to the present work; research grants and personal fees for consulting from AstraZeneca, unrelated to the present work; and research grants from Novartis, Array, Eli Lilly, and Green Cross, unrelated to the present work. ED reports institutional research grants from Incyte Corporation, both related and unrelated to the present work; institutional research grants and honoraria from Boston Medical and Pfizer, unrelated to the present work; honoraria from ARMO, unrelated to the present work; and institutional research grants from Merck, AstraZeneca, GlaxoSmithKline, Medimmune, and OncoMed, unrelated to the present work. DVC reports research grants from Incyte Corporation, related to the present study; and personal fees for consulting from Merck, Bristol-Myers Squibb, Five Prime, Astellas, Taiho, Eli Lilly, Genentech–Roche, Gritstone, Foundation Medicine, Tempus, and Guardant Health, unrelated to the present work. EVC reports personal fees for consulting from Incyte Corporation, both related and unrelated to the present work; personal fees for consulting from Astellas, and AstraZeneca, unrelated to the present work; research grants and personal fees for consulting from Bayer, Bristol-Myers Squibb, Celgene, Eli Lilly, Merck Sharp & Dohme, Merck KGaA, Novartis, Roche, and Servier, unrelated to the present work; and research grants from Amgen, Boehringer Ingelheim, and Ipsen, unrelated to the present work. TJ, CFL, HZ, and LF are employees of, and hold stock in, Incyte Corporation. AV reports personal fees for consulting from Incyte Corporation, both related and unrelated to the present work; and personal fees for consulting from Amgen, AstraZeneca, Roche, Eli Lilly, Bayer, Medac, Delcath, Shire, Beigene, Bristol-Myers Squibb, Celgene, Eisai, Hengrui, Ipsen, Merck, Pieris, QED, Sanofi, and Servier, unrelated to the present work. DG declares no competing interests.
Publisher Copyright:
© 2020 Elsevier Ltd
PY - 2020/5
Y1 - 2020/5
N2 - Background: Fibroblast growth factor receptor (FGFR) 2 gene alterations are involved in the pathogenesis of cholangiocarcinoma. Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3. This study evaluated the safety and antitumour activity of pemigatinib in patients with previously treated, locally advanced or metastatic cholangiocarcinoma with and without FGFR2 fusions or rearrangements. Methods: In this multicentre, open-label, single-arm, multicohort, phase 2 study (FIGHT-202), patients aged 18 years or older with disease progression following at least one previous treatment and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 recruited from 146 academic or community-based sites in the USA, Europe, the Middle East, and Asia were assigned to one of three cohorts: patients with FGFR2 fusions or rearrangements, patients with other FGF/FGFR alterations, or patients with no FGF/FGFR alterations. All enrolled patients received a starting dose of 13·5 mg oral pemigatinib once daily (21-day cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, withdrawal of consent, or physician decision. The primary endpoint was the proportion of patients who achieved an objective response among those with FGFR2 fusions or rearrangements, assessed centrally in all patients who received at least one dose of pemigatinib. This study is registered with ClinicalTrials.gov, NCT02924376, and enrolment is completed. Findings: Between Jan 17, 2017, and March 22, 2019, 146 patients were enrolled: 107 with FGFR2 fusions or rearrangements, 20 with other FGF/FGFR alterations, 18 with no FGF/FGFR alterations, and one with an undetermined FGF/FGFR alteration. The median follow-up was 17·8 months (IQR 11·6–21·3). 38 (35·5% [95% CI 26·5–45·4]) patients with FGFR2 fusions or rearrangements achieved an objective response (three complete responses and 35 partial responses). Overall, hyperphosphataemia was the most common all-grade adverse event irrespective of cause (88 [60%] of 146 patients). 93 (64%) patients had a grade 3 or worse adverse event (irrespective of cause); the most frequent were hypophosphataemia (18 [12%]), arthralgia (nine [6%]), stomatitis (eight [5%]), hyponatraemia (eight [5%]), abdominal pain (seven [5%]), and fatigue (seven [5%]). 65 (45%) patients had serious adverse events; the most frequent were abdominal pain (seven [5%]), pyrexia (seven [5%]), cholangitis (five [3%]), and pleural effusion (five [3%]). Overall, 71 (49%) patients died during the study, most frequently because of disease progression (61 [42%]); no deaths were deemed to be treatment related. Interpretation: These data support the therapeutic potential of pemigatinib in previously treated patients with cholangiocarcinoma who have FGFR2 fusions or rearrangements. Funding: Incyte Corporation.
AB - Background: Fibroblast growth factor receptor (FGFR) 2 gene alterations are involved in the pathogenesis of cholangiocarcinoma. Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3. This study evaluated the safety and antitumour activity of pemigatinib in patients with previously treated, locally advanced or metastatic cholangiocarcinoma with and without FGFR2 fusions or rearrangements. Methods: In this multicentre, open-label, single-arm, multicohort, phase 2 study (FIGHT-202), patients aged 18 years or older with disease progression following at least one previous treatment and an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 recruited from 146 academic or community-based sites in the USA, Europe, the Middle East, and Asia were assigned to one of three cohorts: patients with FGFR2 fusions or rearrangements, patients with other FGF/FGFR alterations, or patients with no FGF/FGFR alterations. All enrolled patients received a starting dose of 13·5 mg oral pemigatinib once daily (21-day cycle; 2 weeks on, 1 week off) until disease progression, unacceptable toxicity, withdrawal of consent, or physician decision. The primary endpoint was the proportion of patients who achieved an objective response among those with FGFR2 fusions or rearrangements, assessed centrally in all patients who received at least one dose of pemigatinib. This study is registered with ClinicalTrials.gov, NCT02924376, and enrolment is completed. Findings: Between Jan 17, 2017, and March 22, 2019, 146 patients were enrolled: 107 with FGFR2 fusions or rearrangements, 20 with other FGF/FGFR alterations, 18 with no FGF/FGFR alterations, and one with an undetermined FGF/FGFR alteration. The median follow-up was 17·8 months (IQR 11·6–21·3). 38 (35·5% [95% CI 26·5–45·4]) patients with FGFR2 fusions or rearrangements achieved an objective response (three complete responses and 35 partial responses). Overall, hyperphosphataemia was the most common all-grade adverse event irrespective of cause (88 [60%] of 146 patients). 93 (64%) patients had a grade 3 or worse adverse event (irrespective of cause); the most frequent were hypophosphataemia (18 [12%]), arthralgia (nine [6%]), stomatitis (eight [5%]), hyponatraemia (eight [5%]), abdominal pain (seven [5%]), and fatigue (seven [5%]). 65 (45%) patients had serious adverse events; the most frequent were abdominal pain (seven [5%]), pyrexia (seven [5%]), cholangitis (five [3%]), and pleural effusion (five [3%]). Overall, 71 (49%) patients died during the study, most frequently because of disease progression (61 [42%]); no deaths were deemed to be treatment related. Interpretation: These data support the therapeutic potential of pemigatinib in previously treated patients with cholangiocarcinoma who have FGFR2 fusions or rearrangements. Funding: Incyte Corporation.
UR - http://www.scopus.com/inward/record.url?scp=85082806833&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85082806833&partnerID=8YFLogxK
U2 - 10.1016/S1470-2045(20)30109-1
DO - 10.1016/S1470-2045(20)30109-1
M3 - Article
C2 - 32203698
AN - SCOPUS:85082806833
VL - 21
SP - 671
EP - 684
JO - The Lancet Oncology
JF - The Lancet Oncology
SN - 1470-2045
IS - 5
ER -