Brief Report: 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 Sub-Study)

Abstract Background S1400D is a biomarker-driven therapeutic sub-study of Lung-MAP evaluating the fibroblast growth factor receptor (FGFR) inhibitor AZD4547 in patients with FGF pathway-activated squamous cell non-small cell lung cancer (SqNSCLC). This is the first phase II trial to evaluate AZD4547 as a targeted approach in patients with previously treated FGFR-altered SqNSCLC 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 1 line of platinum-based systemic therapy. Patients received AZD4547 80 mg twice daily orally. Primary endpoint was response by RECIST 1.1; secondary endpoints included progression-free survival (PFS), overall survival (OS) 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 y (49-88), 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 (AEs) were seen in six patients; one patient had Grade 4 sepsis. Of 27 response evaluable patients, one patient with FGFR3 S249C had unconfirmed partial response with DoR of 1.5 months and one patient with FGFR1 amplification had a confirmed partial response with DoR of 2.9 months (7%, 95% CI 0-17%). Median PFS and OS for the AZD4547–treated cohort were 2.7 mos (95% CI 1.4 - 4.5 mos) and 7.5 mos (95% CI 3.7-9.3 mos). Conclusions AZD4547 had an acceptable safety profile but minimal activity in this predominantly FGFR 1/3 amplified cohort. Evaluation of other targeted agents in Lung-MAP is currently ongoing. ClinicalTrials.gov Identifier: NCT02965378