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J Thorac Oncol. 2019 Jun 11. pii: S1556-0864(19)30462-9. doi: 10.1016/j.jtho.2019.05.041. [Epub ahead of print]

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).

Author information

1
University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: charu.aggarwal@uphs.upenn.edu.
2
SWOG Statistics and Data Management Center at Fred Hutchinson Cancer Research Center, Seattle, Washington.
3
University of California Davis Comprehensive Cancer Center, Sacramento, California.
4
Fox Chase Cancer Center, Philadelphia, Pennsylvania.
5
University of Chicago, Chicago, Illinois.
6
Washington University Medical Center, St. Louis, Missouri.
7
Southeast Clinical Onc Research Consortium NCORP/ Novant Health Presbyterian Medical Center, Charlotte, North Carolina.
8
Sinai Hospital Cancer Institute, Baltimore, Maryland.
9
MD Anderson Cancer Center, Houston, Texas.
10
Yale Cancer Center, New Haven, Connecticut.

Abstract

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.

KEYWORDS:

FGFR inhibitor; LUNG-MAP; SWOG1400

PMID:
31195180
DOI:
10.1016/j.jtho.2019.05.041

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