Abstract 5763
Background
Previous studies indicate that genomic alterations (GAs) in cell-free (cf)DNA are found in > 90% of patients (pts) with mUC [Agarwal et al Cancer 2018]. The ease of collection of cfDNA makes it an attractive alternative to tumor tissue-based screening, but the equivalency of cfDNA and tumor tissue for biomarker testing has yet to be defined in a prospective trial in mUC. We examine this in a phase Ib trial of infigratinib (BGJ398), a potent and selective FGFR1–3 inhibitor, in pts with mUC bearing FGFR3 alterations [Pal et al Cancer Discovery 2018].
Methods
Eligible pts had mUC with activating FGFR3 mutations/fusions and prior platinum-based chemotherapy, unless contraindicated. Pts received infigratinib 125 mg orally daily (3 wks on/1 wk off). Comprehensive genomic profiling (CGP) was performed on FFPE tissues in a CLIA-certified lab (Foundation Medicine; Cambridge, MA), and blood was collected for cfDNA analysis using a 600-gene panel on an Illumina HiSeq 2500 sequencer. Patients were monitored for their best overall response rate (ORR) based on radiological imaging.
Results
67 pts were enrolled; ORR was 25.4% and disease control rate was 64.2%. Blood for cfDNA was collected in 53 pts at the time of screening; collection occurred at a mean of 8.8 days (range 0–37 days) prior to therapy initiation. In contrast, tumor tissue was collected a mean of 520 days (range 28–2315 days) prior. GAs in cfDNA were found in all pts; 38 pts (68%) had detectable FGFR3 mutation. FGFR3 alterations were concordant in 30/38 (79%) of tumors with both tumor tissue and cfDNA at screening. Other commonly encountered alterations were found in KDM6A (30%), KMT2D (20%) and TP53 (20%). In this cohort, all 11 pts with progressive disease (PD) as a best response had detectable FGFR3 in cfDNA at screening, while this was found in only 7/12 responders (58%).
Conclusions
cfDNA identified FGFR3 mutations in 79% of pts whose mutations were previously identified in tumor tissue, suggesting that cfDNA is a secondary screening option for trials assessing FGFR3-directed therapies. The paradoxically higher rate of PD in pts with detectable FGFR3 mutations in cfDNA warrants further study.
Clinical trial identification
NCT01004224.
Editorial acknowledgement
Lee Miller (Miller Medical Communications Ltd).
Legal entity responsible for the study
QED Therapeutics.
Funding
QED Therapeutics.
Disclosure
S.K. Pal: Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Research grant / Funding (self): Medivation; Honoraria (self), Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Aveo; Advisory / Consultancy: Myriad Pharmaceuticals; Advisory / Consultancy: Genentech; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Bristol-Myers Squibb; Advisory / Consultancy: Ipsen; Advisory / Consultancy: Eisai. D.F. Bajorin: Honoraria (self): Merck Sharp & Dohme; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Merck; Advisory / Consultancy, Travel / Accommodation / Expenses: Lilly; Advisory / Consultancy: Fidia Farmaceutici S. p. A.; Advisory / Consultancy: Eisai; Advisory / Consultancy, Travel / Accommodation / Expenses: Urogen pharma; Advisory / Consultancy: Pfizer; Advisory / Consultancy: EMD Serono; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Astellas Pharma; Research grant / Funding (self): Seattle Genetics/Astellas; Research grant / Funding (institution): Dendreon; Research grant / Funding (institution): Amgen; Research grant / Funding (institution): Genentech/Roche. J.H. Hoffman-Censits: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Roche/Genentech; Honoraria (self): Clovis Oncology; Advisory / Consultancy: Foundation medicine; Advisory / Consultancy: AstraZeneca; Research grant / Funding (self): Sanofi. D.I. Quinn: Advisory / Consultancy: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: BMS; Advisory / Consultancy: Dendreon; Advisory / Consultancy: Exelixis; Advisory / Consultancy, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Janssen; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: MSD; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy: Sanofi; Research grant / Funding (institution): Seattle Genetics; Full / Part-time employment: University of Southern California. D.P. Petrylak: Advisory / Consultancy, Research grant / Funding (self): Bayer; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Bellicum Pharmaceuticals; Advisory / Consultancy, Research grant / Funding (self): Dendreon; Advisory / Consultancy, Research grant / Funding (self): Johnson & Johnson; Advisory / Consultancy: Exelixis; Advisory / Consultancy: Ferring; Advisory / Consultancy, Research grant / Funding (self): Millennium; Advisory / Consultancy, Research grant / Funding (self): Medivation; Advisory / Consultancy, Research grant / Funding (self): Pfizer; Advisory / Consultancy, Research grant / Funding (self): Roche; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Sanofi; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Tyme; Advisory / Consultancy, Research grant / Funding (self): Astellas Pharma; Advisory / Consultancy, Research grant / Funding (self): AstraZeneca; Advisory / Consultancy, Research grant / Funding (self): Lilly; Speaker Bureau / Expert testimony: Celgene; Research grant / Funding (self): Progenics; Research grant / Funding (self): Endocyte; Research grant / Funding (self): Genentech; Research grant / Funding (self): Merck; Research grant / Funding (self): Novartis; Research grant / Funding (self): Agensys; Research grant / Funding (self): Innocrin Pharma; Research grant / Funding (self): MedImmune; Research grant / Funding (self): Sotio; Research grant / Funding (self): Seattle Genetics; Research grant / Funding (self): Clovis Oncology. M.D. Galsky: Advisory / Consultancy: BioMotiv; Advisory / Consultancy, Research grant / Funding (institution): Janssen Oncology; Advisory / Consultancy, Research grant / Funding (institution): Dendreon; Advisory / Consultancy, Research grant / Funding (institution): Merck; Advisory / Consultancy: GlaxoSmithKline; Advisory / Consultancy: Lilly; Advisory / Consultancy: Astellas; Research grant / Funding (institution): Genentech/Roche; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Advisory / Consultancy, Research grant / Funding (institution): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: EMD Serono; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Seattle Genetics; Advisory / Consultancy: Incyte; Advisory / Consultancy: Aileron Therapeutics; Advisory / Consultancy: Dracen; Advisory / Consultancy: Inovio Pharmaceuticals; Advisory / Consultancy: NuMab; Licensing / Royalties, Methods and Compositions for Treating Cancer and Related Methods: Mount Sinai School of Medicine; Advisory / Consultancy: Genentech; Shareholder / Stockholder / Stock options: Rappta Therapeutics. U.N. Vaishampayan: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Pfizer; Honoraria (self): Janssen; Honoraria (self), Research grant / Funding (self): Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer; Honoraria (self), Speaker Bureau / Expert testimony: Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Bristol-Myers Squibb; Advisory / Consultancy, Speaker Bureau / Expert testimony: Genentech/Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Exelixis; Advisory / Consultancy, Research grant / Funding (self): Astellas Pharma; Honoraria (self): Genentech. U. De Giorgi: Advisory / Consultancy, Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy: Astellas Pharma; Advisory / Consultancy, Research grant / Funding (institution): Sanofi; Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Advisory / Consultancy: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Ipsen; Advisory / Consultancy: Merck; Research grant / Funding (institution): AstraZeneca; Research grant / Funding (institution): Roche. S. Gupta: Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): Viralytics; Research grant / Funding (institution): Hoosier Cancer Research Network; Research grant / Funding (institution): Rexahn Pharmaceuticals; Research grant / Funding (institution): Five Prime Therapeutics; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): MedImmune; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Clovis Oncology; Research grant / Funding (institution): LSK; Spouse / Financial dependant: Keryx; Spouse / Financial dependant: Salarius Pharmaceuticals. H.A. Burris: Advisory / Consultancy, Research grant / Funding (institution): Mersana; Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy: Forma Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Novartis; Advisory / Consultancy, Research grant / Funding (institution): Roche/Genentech; Advisory / Consultancy, Research grant / Funding (institution): TG Therapeutics; Advisory / Consultancy, Research grant / Funding (institution): MedImmune; Advisory / Consultancy, Research grant / Funding (institution): Bristol-Myers Squibb; Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment: HCA Healthcare / Sarah Cannon; Research grant / Funding (institution): Incyte; Research grant / Funding (institution): Tarveda Therapeutics; Research grant / Funding (institution): Macrogenics; Research grant / Funding (institution): Boehringer Ingelheim; Research grant / Funding (institution): Lilly; Research grant / Funding (institution): Seattle Genetics; Research grant / Funding (institution): AbbVie; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Celldex; Research grant / Funding (institution): Merck; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): Agios; Research grant / Funding (institution): Jounce Therapeutics; Research grant / Funding (institution): Moderna Therapeutics; Research grant / Funding (institution): CytomX Therapeutics; Research grant / Funding (institution): GlaxoSmithKline; Research grant / Funding (institution): Verastem; Research grant / Funding (institution): Tesaro; Research grant / Funding (institution): Immunocore; Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Millennium; Research grant / Funding (institution): BioMed Valley Discoveries; Research grant / Funding (institution): Pfizer; Research grant / Funding (institution): PTC Therapeutics; Research grant / Funding (institution): Loxo; Research grant / Funding (institution): Vertex; Research grant / Funding (institution): eFFECTOR Therapeutics; Research grant / Funding (institution): Gilead Sciences; Research grant / Funding (institution): Valent Technologies; Research grant / Funding (institution): BioAtla; Research grant / Funding (institution): CicloMed; Research grant / Funding (institution): Harpoon therapeutics; Research grant / Funding (institution): Jiangsu Hengrui Medicine; Research grant / Funding (institution): Revolution Medicines; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): H3 Biomedicine; Research grant / Funding (institution): Neon Therapeutics; Research grant / Funding (institution): OncoMed; Research grant / Funding (institution): Regeneron; Research grant / Funding (self): Sanofi. H.S. Soifer: Shareholder / Stockholder / Stock options, Full / Part-time employment: bioTheranostics; Shareholder / Stockholder / Stock options, Full / Part-time employment: QED Therapeutics. G. Li: Full / Part-time employment: QED Therapeutics. C.L. Dambkowski: Full / Part-time employment: QED Therapeutics. S. Moran: Full / Part-time employment: QED Therapeutics. H. Wang: Full / Part-time employment: QED Therapeutics. J.E. Rosenberg: Honoraria (self): UpToDate; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (self): AstraZeneca; Honoraria (self): Medscape; Honoraria (self): Vindico; Honoraria (self): Peerview; Honoraria (self): Chugai Pharma; Advisory / Consultancy: Lilly; Advisory / Consultancy, Shareholder / Stockholder / Stock options: Merck; Advisory / Consultancy, Research grant / Funding (institution): Agensys; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Roche/Genentech; Advisory / Consultancy: Sanofi; Advisory / Consultancy: AstraZeneca/MedImmune; Advisory / Consultancy: EMD Serono; Advisory / Consultancy, Research grant / Funding (institution): Seattle Genetics; Advisory / Consultancy, Research grant / Funding (institution): Bayer; Advisory / Consultancy: Inovio Pharmaceuticals; Advisory / Consultancy: BioClin Therapeutics; Advisory / Consultancy: QED Therapeutics; Advisory / Consultancy: Adicet Bio; Advisory / Consultancy: Sensei Biotherapeutics; Advisory / Consultancy: Fortress Biotech; Advisory / Consultancy: Pharmacyclics; Advisory / Consultancy: western oncolytics; Research grant / Funding (self): Incyte; Research grant / Funding (institution): Genentech; Research grant / Funding (institution): Oncogenex; Research grant / Funding (institution): Mirati Therapeutics; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Viralytics; Shareholder / Stockholder / Stock options: Illumina; Licensing / Royalties, Institution: Predictor of platinum sensitivity. All other authors have declared no conflicts of interest.
Resources from the same session
2344 - Lung Cancer in Europe: strengthening policy responses to address unmet needs
Presenter: Mary Bussell
Session: Poster Display session 3
Resources:
Abstract
1359 - Curative treatment timelines for breast, colorectal, lung and prostate cancer: Implications for medical leave coverage
Presenter: Selina Wong
Session: Poster Display session 3
Resources:
Abstract
4433 - Acute Diagnostic Oncology Clinic: A Unique Primary Care-Oncology Service
Presenter: Abhijit Gill
Session: Poster Display session 3
Resources:
Abstract
3506 - THE NEW MUTATIONAL MODEL IN ONCOLOGY. What changes in welfare, clinical practice, research, and regulatory procedures
Presenter: Nicola Normanno
Session: Poster Display session 3
Resources:
Abstract
3350 - Selection of a set of quality indicators (QI) for oncological clinical pathway
Presenter: Aude Fourcade
Session: Poster Display session 3
Resources:
Abstract
4400 - Sustainable drug prices at market launch: policy proposals and their empirical evidence
Presenter: Nora Fanzen
Session: Poster Display session 3
Resources:
Abstract
4118 - Impact of financial considerations on French physicians’ prescription choices for advanced non-small cell lung cancer (NSCLC)
Presenter: Nathalie Olympios
Session: Poster Display session 3
Resources:
Abstract
1340 - The direct medical cost of breast cancer in a Belgian hospital
Presenter: Hannan Lemhouer
Session: Poster Display session 3
Resources:
Abstract
1863 - Does the healthcare system approaches cancer patients for using private services during diagnostic process?
Presenter: Karolina Osowiecka
Session: Poster Display session 3
Resources:
Abstract
2637 - Measuring financial toxicity of cancer in the Italian health care system: initial results of the patient reported outcome for Fighting Financial Toxicity of cancer project (proFFiT).
Presenter: Silvia Riva
Session: Poster Display session 3
Resources:
Abstract