A Phase Ib Open-Label Multicenter Study of AZD4547 in Patients with Advanced Squamous Cell Lung Cancers

Paul K Paik, Ronglai Shen, Michael F Berger, David Ferry, Jean-Charles Soria, Alastair Mathewson, Claire Rooney, Neil R Smith, Marie Cullberg, Elaine Kilgour, Donal Landers, Paul Frewer, Nigel Brooks, Fabrice André

Research output: Contribution to journalArticlepeer-review


Purpose: Squamous cell lung cancers (SQCLC) account for 25% of all NSCLCs, yet the prognosis of these patients is poor and treatment options are limited. Amplified FGFR1 is one of the most common oncogenic events in SQCLCs, occurring in approximately 20% of cases. AZD4547 is a potent and selective FGFR1-3 inhibitor with antitumor activity in FGFR1-amplified SQCLC cell lines and patient-derived xenografts.Experimental Design: On the basis of these data, we performed a phase I study of AZD4547 in patients with previously treated stage IV FGFR1-amplified SQCLCs (NCT00979134). FGFR1 amplification (FGFR1:CEP8 ≥ 2) was determined by FISH. The primary endpoint was safety/tolerability. Secondary endpoints included antitumor activity, pharmacokinetics, pharmacodynamics, and molecular analyses.Results: Fifteen FGFR1-amplified patients were treated. The most common related adverse events (AE) were gastrointestinal and dermatologic. Grade ≥3-related AEs occurred in 3 patients (23%). Thirteen patients were evaluable for radiographic response assessment. The overall response rate was 8% (1 PR). Two of 15 patients (13.3%) were progression-free at 12 weeks, and the median overall survival was 4.9 months. Molecular tests, including next-generation sequencing, gene expression analysis, and FGFR1 immunohistochemistry, showed poor correlation between gene amplification and expression, potential genomic modifiers of efficacy, and heterogeneity in 8p11 amplicon.Conclusions: AZD4547 was tolerable at a dosage of 80 mg oral twice a day, with modest antitumor activity. Detailed molecular studies show that these tumors are heterogeneous, with a range of mutational covariates and stark differences in gene expression of the 8p11 amplicon that likely explain the modest efficacy of FGFR inhibition in this disease. Clin Cancer Res; 23(18); 5366-73. ©2017 AACR.

Original languageEnglish
Pages (from-to)5366-5373
Number of pages8
JournalClinical cancer research : an official journal of the American Association for Cancer Research
Issue number18
Publication statusPublished - 15 Sept 2017


  • Aged
  • Antineoplastic Agents/administration & dosage
  • Benzamides/administration & dosage
  • Carcinoma, Squamous Cell/drug therapy
  • Chromosomes, Human, Pair 8
  • Female
  • Gene Amplification
  • Gene Expression Profiling
  • Genetic Heterogeneity
  • Humans
  • Lung Neoplasms/drug therapy
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Piperazines/administration & dosage
  • Pyrazoles/administration & dosage
  • Receptor, Fibroblast Growth Factor, Type 1/genetics
  • Sequence Analysis, DNA
  • Treatment Outcome

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


Dive into the research topics of 'A Phase Ib Open-Label Multicenter Study of AZD4547 in Patients with Advanced Squamous Cell Lung Cancers'. Together they form a unique fingerprint.

Cite this