TY - JOUR
T1 - SWOG S1400D (NCT02965378), a Phase II Study of the Fibroblast Growth Factor Receptor Inhibitor AZD4547 in Previously Treated Patients With Fibroblast Growth Factor Pathway–Activated Stage IV Squamous Cell Lung Cancer (Lung-MAP Substudy)
AU - Aggarwal, Charu
AU - Redman, Mary W.
AU - Lara, Primo N.
AU - Borghaei, Hossein
AU - Hoffman, Philip
AU - Bradley, Jeffrey D.
AU - Newman, Alfred J.
AU - Feldman, Marvin J.
AU - Minichiello, Katherine
AU - Miao, Jieling
AU - Mack, Philip C.
AU - Papadimitrakopoulou, Vassiliki A.
AU - Herbst, Roy S.
AU - Kelly, Karen
AU - Gandara, David R.
N1 - Funding Information:
This research supported in part by National Institutes of Health / National Cancer Institute grants CA180888 , CA180819 , CA180820 , CA180821 , CA180868 , CA189858 , CA189861 , CA189830 , CA189821 , CA180858 , CA189971 , CA189972 , CA180826 , CA189822 , and CA180798 ; and by Amgen , Astra Zeneca , Bristol-Myers Squibb Company, Genentech , and Pfizer through the Foundation for the National Institutes of Health , in partnership with Friends of Cancer Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health .
Funding Information:
Disclosure: Dr. Aggarwal has received personal fees from Bristol-Myers Squibb, Celgene, Roche/Genentech, and Astra Zeneca. Dr. Lara has received grants from Millennium, Polaris, GlaxoSmithKline, Genentech, Aragon Pharmaceuticals, Janssen Biotech, Heat Biologics, TRACON Pharma, Merck, Pharmacyclics, and Incyte; and has received personal fees from Exelixis, Pfizer, Astra Zeneca, Bayer, Genentech/Roche, Janssen, Bristol-Myers Squibb, AbbVie, Turnstone Bio, Foundation Medicine, Merck, Cell/Max Life, and Nektar. Dr. Borghaei has recived grants from Bristol-Myers Squibb, Lilly, Celgene, Merck, and Millennium; and has received personal fees from Bristol-Myers Squibb, Lilly, Genentech, Celgene, EMD Serono, Merck, Pfizer, Boehringer Ingelheim, Astra Zeneca, Genmab, Novartis, Regeneron, BioNTech, Cantargia AB, Amgen, AbbVie, Asiom, and Takeda. Dr. Bradley has received grants from Mevion Medical Systems, Inc.; and has received personal fees from Astra Zeneca, Inc., Mevio Medical Systems, Inc., and ViewRay, Inc. Dr. Feldman has received personal fees from Boehringer Ingelheim, Lilly Pharmaceuticals, and Bristol-Myers Squibb. Dr. Mack has received grants from Boehringer Ingelheim; and has received personal fees from Astra Zeneca, Guardant Health, and Pfizer. Dr. Papadimitrakopoulou has received grants from Eli Lilly, Novartis, Merck, Astra Zeneca, F. Hoffman?La Roche, Nektar Therapeutics, Janssen, Bristol-Myers Squibb, Checkmate, and Incyte; and has received personal fees from Nektar Therapeutics, Astra Zeneca Pharmaceuticals, Arrys Therapeutics, Merck, Loxo Oncology, ARAXES Pharma, F. Hoffmann-La Roche, Janssen Research Foundation, Bristol-Myers Squibb, Clovis Oncology, Eli Lilly, Novartis, Takeda, AbbVie, Tesaro Exelixis, and Gritsone. Dr. Herbst has received grants from Astra Zeneca, Eli Lilly and Company, and Merck and Company; and has received personal fees from AbbVie Pharmaceuticals, Astra Zeneca, Biodesix, Bristol-Myers Squibb, Eli Lilly and Company, EMD Serrano, Genentech/Roche, Heat Biologics, Jun Shi Pharmaceuticals, Loxo Oncology, Merck and Company, Nektar. NextCure, Novartis, Pfizer, Sanofi, Seattle Genetics, Shire PLC, Spectrum Pharmaceuticals, Symphogen, Tesaro, Neon Therapeutics, and Infinity Pharmaceuticals. Dr. Kelly has received personal fees from Astra Zeneca. Dr. Gandara has received grants from Astra Zeneca. The remaining authors declare no conflict of interest.This research supported in part by National Institutes of Health/National Cancer Institute grants CA180888, CA180819, CA180820, CA180821, CA180868, CA189858, CA189861, CA189830, CA189821, CA180858, CA189971, CA189972, CA180826, CA189822, and CA180798; and by Amgen, Astra Zeneca, Bristol-Myers Squibb Company, Genentech, and Pfizer through the Foundation for the National Institutes of Health, in partnership with Friends of Cancer Research. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2019 International Association for the Study of Lung Cancer
PY - 2019/10
Y1 - 2019/10
N2 - Background: S1400D is a biomarker-driven therapeutic substudy of Lung-MAP evaluating the fibroblast growth factor (FGF) receptor (FGFR) inhibitor AZD4547 in patients with FGF pathway-activated squamous cell. This is the first phase II trial to evaluate AZD4547 as a targeted approach in patients with previously treated FGFR-altered squamous cell NSCLC and is the first demonstration of successful implementation and conduct of a national umbrella protocol in this disease setting. Methods: Eligible patients had tumoral FGFR alteration or mutation and had progressive disease after at least one line of platinum-based systemic therapy. Patients received AZD4547 80 mg twice daily orally. Primary endpoint was response by Response Evaluation Criteria in Solid Tumors version 1.1; secondary endpoints included progression-free survival, overall survival, and duration of response (DoR). Results: Ninety-two patients were assigned to S1400D, 43 were enrolled, and 27 AZD4547-treated patients were evaluable. Evaluable patients were predominantly white (n = 24, 89%), median age 66 years (range, 49–88 years old), and female (n = 7, 26%). FGFR alterations included FGFR1 amplification (n = 23; 85%), FGFR3 amplification (n = 2; 7%), FGFR3 S249C (n = 2; 7%), and FGFR3 fusion (n = 1; 4%). Treatment with ADZ4547 was well tolerated; grade 3 adverse events occurred in six patients, and one patient had grade 4 sepsis. Of 27 response-evaluable patients, 1 patient with FGFR3 S249C had unconfirmed partial response with a DoR of 1.5 months and 1 patient with FGFR1 amplification had a confirmed partial response with a DoR of 2.9 months (7%, 95% confidence interval [CI]: 0%–17%). Median progression-free survival and overall survival for the AZD4547-treated cohort were 2.7 months (95% CI: 1.4– 4.5 months) and 7.5 months (95% CI: 3.7–9.3 months). Conclusions: AZD4547 had an acceptable safety profile but minimal activity in this predominantly FGFR1/FGFR3–amplified cohort. Evaluation of other targeted agents in Lung-MAP is ongoing.
AB - Background: S1400D is a biomarker-driven therapeutic substudy of Lung-MAP evaluating the fibroblast growth factor (FGF) receptor (FGFR) inhibitor AZD4547 in patients with FGF pathway-activated squamous cell. This is the first phase II trial to evaluate AZD4547 as a targeted approach in patients with previously treated FGFR-altered squamous cell NSCLC and is the first demonstration of successful implementation and conduct of a national umbrella protocol in this disease setting. Methods: Eligible patients had tumoral FGFR alteration or mutation and had progressive disease after at least one line of platinum-based systemic therapy. Patients received AZD4547 80 mg twice daily orally. Primary endpoint was response by Response Evaluation Criteria in Solid Tumors version 1.1; secondary endpoints included progression-free survival, overall survival, and duration of response (DoR). Results: Ninety-two patients were assigned to S1400D, 43 were enrolled, and 27 AZD4547-treated patients were evaluable. Evaluable patients were predominantly white (n = 24, 89%), median age 66 years (range, 49–88 years old), and female (n = 7, 26%). FGFR alterations included FGFR1 amplification (n = 23; 85%), FGFR3 amplification (n = 2; 7%), FGFR3 S249C (n = 2; 7%), and FGFR3 fusion (n = 1; 4%). Treatment with ADZ4547 was well tolerated; grade 3 adverse events occurred in six patients, and one patient had grade 4 sepsis. Of 27 response-evaluable patients, 1 patient with FGFR3 S249C had unconfirmed partial response with a DoR of 1.5 months and 1 patient with FGFR1 amplification had a confirmed partial response with a DoR of 2.9 months (7%, 95% confidence interval [CI]: 0%–17%). Median progression-free survival and overall survival for the AZD4547-treated cohort were 2.7 months (95% CI: 1.4– 4.5 months) and 7.5 months (95% CI: 3.7–9.3 months). Conclusions: AZD4547 had an acceptable safety profile but minimal activity in this predominantly FGFR1/FGFR3–amplified cohort. Evaluation of other targeted agents in Lung-MAP is ongoing.
KW - FGFR inhibitor
KW - LUNG-MAP
KW - SWOG1400
UR - http://www.scopus.com/inward/record.url?scp=85069576973&partnerID=8YFLogxK
U2 - 10.1016/j.jtho.2019.05.041
DO - 10.1016/j.jtho.2019.05.041
M3 - Article
C2 - 31195180
AN - SCOPUS:85069576973
SN - 1556-0864
VL - 14
SP - 1847
EP - 1852
JO - Journal of Thoracic Oncology
JF - Journal of Thoracic Oncology
IS - 10
ER -