1384TiP - Prospective comparison of liquid biopsy to standard of care tissue testing in metastatic, non-squamous, non-small cell lung cancer (NSCLC) patients...

Date 09 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Cancer in Adolescents
Non-Small-Cell Lung Cancer, Metastatic
Lung and other Thoracic Tumours
Pathology/Molecular Biology
Translational Research
Presenter Ramon Palmero
Citation Annals of Oncology (2017) 28 (suppl_5): v460-v496. 10.1093/annonc/mdx380
Authors R. Palmero1, Á. Taus2, M. Majem Tarruella3, S. Viteri4, E. Carcereny Costa5, J. Garde6, J. Garde7, E. Felip Font8, C. Cassidy9, D. Dix9, N. Karachaliou4, R. Rosell4
  • 1Medical Oncology, Catalan Institute of Oncology, 08907 - L'Hospitalet/ES
  • 2Oncology, del Mar Hospital, 8003 - Barcelona/ES
  • 3Medical Oncology, Santa Creu i Sant Pau Hospital, 8026 - Barcelona/ES
  • 4Oncology, Institute of Oncology Dr. Rosell (Dexeus University Hospital QuironSalud Group), 80280 - Barcelona/ES
  • 5Medical Oncology, Can Ruti Hospital, 08916 - Barcelona/ES
  • 6Medical Oncology, Arnau de Vilanova University Hospital, Valencia/ES
  • 7Scientific, Medica Scientia Innovation Research-MEDSIR, 08007 - Barcelona/ES
  • 8Medical Oncology Service (lung Cancer Unit)  , Vall d'Hebrón University Hospital  , 08035 - Barcelona/ES
  • 9Clinical Development, Guardant Health, Inc., Redwood City/US

Abstract

Background

Targeted therapy improves clinical outcomes in pts with advanced NSCLC harboring specific genetic alterations. Guidelines recommend tissue-based assessment of markers, but this approach may be limited by access to sufficient tissue and tumor heterogeneity, making it difficult to identify all pts who may benefit from these treatments. An alternative approach is to assess somatic mutations in circulating cell-free tumor DNA (cfDNA). The aim of this study is to demonstrate that cfDNA is non-inferior to tissue-based genotyping in detecting clinically actionable tumor biomarkers in pts with newly diagnosed metastatic non-squamous NSCLC.

Trial design

This is a multi-center, prospective, single-cohort study. Major inclusion criteria are: (1) metastatic, biopsy proven, non-squamous NSCLC, (2) candidate for first line systematic therapy, (3) no prior targeted therapy. Peripheral blood (20 mL) is collected for cfDNA sequencing prior to and 2 weeks after treatment initiation and at the time of disease progression (maximum 12 months follow-up). cfDNA sequencing is performed using Guardant360, a comprehensive next-generation assay (Guardant Health, Inc., Redwood City, CA USA). Pre-treatment tissue samples archived at local sites are centrally analyzed. Pts are treated according to investigator standard of care criteria. Tumor response is assessed centrally per RECIST v1.1 on pts who received targeted therapy. Primary endpoint is the detection rate, in either blood or tissue, of a clinically actionable somatic biomarker, defined as mutations in EGFR, BRAF, MET and ERBB2, copy number of MET and rearrangement of the ROS1, RET and ALK genes. A total of 182 pts are needed to test a 10% non-inferiority margin. We assumed a 20% detection rate, with a 19% discordant pairs and 10% dropout rate. The one-sided asymptotic test has 90% power, at a nominal significance level of 5%. Secondary objectives are to compare turn-around time, time to treatment initiation, rates of insufficient tissue for testing or tumor not detected in cfDNA, and tumor response to targeted therapies. Genomically acquired resistance to targeted therapies is also investigated.

Clinical trial identification

MedOPP125 (NCT number in progress)

Legal entity responsible for the study

Medica Scientia Innovation Research-MEDSIR

Funding

Guardant Health Inc.

Disclosure

S. Viteri: Research: AbbVie, ARIAD, Astex, AZ/MedImmune, Boehringer, Clovis, CytRx, Daiichi Sankyo, GSK, Hanmi, Incyte, Merck, Novartis, Pfizer, Puma, Roche, Servier, Vaxon. Advisor: Boehringer, Clovis, Idea Pharma, Novartis, Promega Biotech, Roche, Targovax. E. Felip Font: Personal fees (Consulting fees) from: Boehringer Ingelheim, Eli Lilly, Pfizer, Roche and MSD, Astra Zeneca and Bristol Myers Squibb. All other authors have declared no conflicts of interest.