On April 19, 2018 Personal Genome Diagnostics Inc. (PGDx) reported that its wholeexome analysis platform contributed to an important new study published in the New England Journal of Medicine (NEJM) showing promising efficacy for a leading checkpoint inhibitor in early stage lung cancer (Press release, Personal Genome Diagnostics, APR 19, 2018, View Source [SID1234525533]).1 The study also showed that patients who had higher tumor mutation burden (TMB) according to the PGDx analysis had better responses to the checkpoint inhibitor than those with lower tumor mutation loads. The study was conducted by cancer researchers from Johns Hopkins University, including PGDx co-founder Victor Velculescu, MD, PhD, and the Memorial Sloan Kettering Cancer Center (MSK). Earlier this year, PGDx announced an agreement with MSK for developing, registering and commercializing products and services that include tumor mutation burden biomarker status.
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The NEJM study reported that non-small cell lung cancer (NSCLC) patients who received the anti-PD-1 agent nivolumab before undergoing surgery for their cancer experienced fewer relapses than patients who did not.
The nivolumab-treated patients also showed signs of anti-tumor immunity stimulated by the immuno-oncology
therapy. Importantly, the study showed a direct correlation between TMB and checkpoint inhibitor response– patients with higher mutation burden scores as measured by the PGDx platform had a better response to
nivolumab—the more tumor mutations, the better the response. TMB scores were even better predictors of
response to nivolumab than measurements of PD-1 itself.
John Simmons, PhD, Director of Translational Science at PGDx, commented, "We are proud that our pioneering
work in whole exome analysis has made our platform a standard for many in the field of oncology. The analysis
generated using the PGDx exome platform (shown in Figure 3 in the NEJM study) shows a striking correlation
between tumor mutation load and response to immune checkpoint blockade. We believe that the high-quality
mutation detection approach developed at PGDx, including our proprietary VariantDxTM bioinformatics pipeline,
contributed to the strength of the results."
Dr. Simmons added, "This study also highlights the clinical relevance of TMB, even in early stage disease prior
to therapy. Whole exome analysis has been the ‘gold standard’ driving the field’s understanding of how mutation
load affects clinical response to checkpoint blockade, but it isn’t currently practical for routine clinical use. Our
ongoing initiative to translate our expertise and research applications into standardized IVD testing products for
measuring TMB and other cancer biomarkers is intended to ensure wide accessibility and use of these tools by
drug developers and physicians."
"This study is an excellent example of how the advanced scientific work of our distinguished founders gives us
the opportunity to contribute to groundbreaking cancer research while reinforcing our credibility with our industry
partners," said Doug Ward, CEO of Personal Genome Diagnostics. "Our leading VariantDx bioinformatics
analysis pipeline that informed this study and fuels our PGDx assays has allowed PGDx to be a leader in
immuno-oncology testing. We look forward to working with our growing network of partners to deliver accurate,
accessible diagnostic tests that indicate the most effective therapies for patients–an essential part of the
genomic revolution that is transforming cancer treatment."
PGDx has expertise in cancer genome analysis ranging from sample preparation and sequencing to data
interpretation and analysis. The company uses next-generation sequencing (NGS) and its proprietary algorithms
to identify alterations in complex cancer genomics and has developed novel technologies for non-invasive
approaches to cancer diagnostics. PGDx is also developing and will commercialize a portfolio of clinically
validated, regulated tissue and liquid biopsy cancer tests, enabling worldwide access to standardized NGS
testing.
1 – Neoadjuvant PD-1 Blockade in Resectable Lung Cancer, P.M. Forde, J.E. Chaft, K.N. Smith, V. Anagnostou, T.R.
Cottrell, M.D. Hellmann, M. Zahurak, S.C. Yang, D.R. Jones, S. Broderick, R.J. Battafarano, M.J. Velez, N. Rekhtman, Z.
Olah, J. Naidoo, K.A. Marrone, F. Verde, H. Guo, J. Zhang, J.X. Caushi, H.Y. Chan, J.-W. Sidhom, R.B. Scharpf, J. White, E.
Gabrielson, H. Wang, G.L. Rosner, V. Rusch, J.D. Wolchok, T. Merghoub, J.M. Taube, V.E. Velculescu, S.L. Topalian, J.R.
Brahmer, and D.M. Pardoll, New England Journal of Medicine, April 16, 2018