Abstract 5884
Background
Due to the compelling predictive value of companion diagnostic (CDx) biomarkers tied to targeted and immune-based therapies, well-characterized robust analytic and clinical validation of genomic assays has become mandatory. An NGS-based CGP (comprehensive genomic profiling) platform was developed in compliance with FDA guidelines for CDx indications.
Methods
DNA extracted from FFPE tumor tissue underwent whole-genome shotgun library construction and hybridization-based capture, followed by sequencing using Illumina HiSeq 4000. Sequence data were processed using a proprietary analysis pipeline designed to identify sub substitutions, indels, copy number alterations, genomic rearrangements, microsatellite instability (MSI), and tumor mutational burden (TMB) in 324 genes.
Results
Clinical validity was demonstrated by establishing statistical non-inferiority between CGP and the respective approved CDx, e.g. cobas EGFR and BRAF mutational testing, ALK rearrangements with FISH and IHC, ERBB2 amplification with FISH, and others. For analytical validity, concordance with an orthogonal NGS platform was 94.6% for substitutions and indels, and within-assay reproducibility had positive percent agreement (PPA) of 99.4%. TMB was analytically validated via concordance with whole-exome sequencing. For the first 616 patients (25% non-small cell lung cancer) assayed in clinical care, 6.8% of cases had TMB exceeding 20 mut/Mb, with 25% of these also harboring microsatellite instability. For 143 NSCLC cases, >50% harbored 10 mut/Mb. Of 354 cases with CDx findings possible, 25.6% had such findings, which were split nearly evenly between indications to benefit from and contraindications to targeted therapies.
Conclusions
We developed a CGP assay and demonstrated clinical and analytical validity for CDx biomarkers for targeted therapy, with clinical validation for TMB in progress via correlation with prospective immunotherapy trials. Initial oncologist feedback indicates impact of assay results on course of treatment decisions in patient care.
Clinical trial identification
Legal entity responsible for the study
Foundation Medicine, Inc.
Funding
Foundation Medicine, Inc.
Editorial Acknowledgement
Disclosure
Y. Li: Employee of and stockholder: Foundation Medicine Inc. J.X. Sun: Stockholder: Foundation Medicine Inc. J. Skoletsky, C. Milbury, C. Burns, W-K. Yip, N. Dewal, J. He, J. Tuesdell, J.A. Elvin, G. Otto, D. Lipson, J.S. Ross, V.A. Miller, M. Doherty, C. Vietz: Employee and stockholder: Foundation Medicine Inc. E. Peters, E. Schleifman, J. Noe: Employee and stockholder: Genentech Inc. S. Jenkins: Employee and stockholder: AstraZeneca.
Resources from the same session
5877 - TCR beta chain convergence defines the tumor infiltrating T cell repertoire of melanoma and non-small cell lung carcinoma.
Presenter: Timothy Looney
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
3212 - PI3K inhibition and modulation of immune and tumor microenvironment markers by copanlisib in patients with non-Hodgkin's lymphoma or advanced solid tumors
Presenter: Ahmad Awada
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
3574 - Pan-squamous genomic profiling stratified by anatomic tumor site and viral association
Presenter: Meagan Montesion
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
4113 - Toward the Standardization of Bioinformatics Methods for the Accurate Assessment of Tumor Mutational Burden (TMB)
Presenter: Han Chang
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
4468 - Prediction of primary resistance to anti-PD1 therapy (APD1) in 2nd line NSCLC
Presenter: Egbert Smit
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
4570 - Immunomodulatory germline variation impacts the development of multiple primary melanoma (MPM).
Presenter: Robert Ferguson
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
1169 - Leukocyte telomere length and recurrence risk after EGFR-TKIs therapy in patients with advanced lung adenocarcinoma
Presenter: Ming Yang
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
1707 - Gene embedding: a novel machine learning approach to identify gene candidates related to immunotherapy responsiveness
Presenter: Chi Tung Choy
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
2123 - Common and rare DPYD variants are predictive for 5FU/capecitabine (5FU) toxicity: The MRC COIN and COIN-B trials
Presenter: Ayman Madi
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract
5671 - The landscape of NTRK fusions in Chinese solid tumor patients
Presenter: Qi Ling
Session: Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research
Resources:
Abstract