On February 19, 2020 NantHealth, Inc. (NASDAQ: NH), a next-generation, evidence-based, personalized healthcare company and NantOmics, LLC, the leader in molecular analysis, reported Real-world data for differential expression of immunoregulatory molecules and targetable cancer genes may provide therapeutic insights into agnostic-driven trial designs during an oral presentation at the Real World Evidence in Immunotherapy Session at the Clinical Immuno-Oncology Symposium, sponsored by the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) and the Society for Immunotherapy in Cancer (SITC) (Free SITC Whitepaper) (Press release, NantHealth, FEB 19, 2020, View Source [SID1234554509]).
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"Our analysis shows that commonly evaluated mutations are associated with therapeutic targets for immunotherapy," said Sandeep "Bobby" Reddy, MD, Chief Medical Officer, NantHealth. "For example we saw high IDO expression in in patient samples with FBXW7 mutations. IDO has failed in clinical trials in the past but perhaps the wrong patient population was assessed. This data may help design better clinical trials which match the molecular phenotype with the best possible combination of therapies."
IDO1 (i.e. IDO) is the molecular target for several immunotherapy drugs (e.g. Epacadostat) that have failed in trials that selected patients based on tissue-type. FBXW7 mutants are significantly higher in IDO1 expression regardless of which tissue they show up in, and FXBW7 mutations are found in many tissue types. Agnostic-driven clinical trial designs using strategies to identify FBXW7 tumors that have higher expression of IDO1 may be a good strategy for these types of drugs.
In the study, authors utilized TCGA data and data collected from NantHealth’s GPS Cancer database on whole exome (WES) DNA tumor and paired normal and matched deep whole transcriptomic sequencing (RNA-Seq) to identify novel associations between oncogenic mutations and immune checkpoint therapeutic targets.
"CDKN2A mutation status was identified as associated with increased PD1 and CTLA4 expression while KRAS and APC mutations were assessed as associated with decreased PDL1/2 expression," said Christopher Szeto, Director of Machine Learning. "These mutation associations remained significant after accounting for tissue-specific expression patterns."
Title: "Real-world data validation for differential expression of immunoregulatory molecules and targetable cancer genes may provide therapeutic insights into agnostic-driven trial designs," Abstract #10
Authors: Jacob J. Adashek, Christopher Szeto, Sandeep K. Reddy, Philippe E. Spiess
Poster Session and Number:
Who: NantHealth, Inc. and NantOmics, LLC
What: Real World Evidence in Immunotherapy Session
When: February 6-8, 2020
Location: Rosen Shingle Creek