August 22, 2018

MolecularMD Launches Validated Tumor Mutation Burden Assay for Immuno-Oncology Clinical Trial Services

PORTLAND, OR – August 22, 2018 – MolecularMD today announces it has validated Thermo Fisher Scientific’s Oncomine™ Tumor Mutation Load Assay for clinical research trials to aid immunotherapy drug development programs for the pharmaceutical industry. The latest approach in the evolving field of immuno-oncology, tumor mutation burden (TMB) analysis is rapidly becoming an independent predictor for patient stratification and response to immunotherapies, such as checkpoint inhibitors.

“The methods used so far to assess tumor mutation burden in clinical studies have included whole exome sequencing and several laboratory-developed, targeted next-generation sequencing panels,” said Cindy Spittle, Ph.D., Vice President Development & Scientific Affairs at MolecularMD. “But in order to fully determine the value of TMB as a predictive biomarker, a standardized panel, workflow and data analysis pipeline for TMB assessment is needed.”

Thermo Fisher’s Oncomine Tumor Mutation Load Assay interrogates 409 cancer-related genes, spanning ~1.7 megabases (Mb) of the genome using as little as 20 nanograms of formalin-fixed paraffin-embedded (FFPE) tumor DNA in a three-day workflow. The assay highly correlates with exome mutation counts, thereby obviating the need for whole-exome sequencing, and allows for a higher percentage of samples to be evaluated. TMB is calculated in tumor DNA samples without the need for including a matched normal sample with a streamlined Ion Reporter workflow.

Sample quantity and quality requirements were key considerations for MolecularMD’s selection of an assay suitable for clinical research studies and potential diagnostic application. To that end, MolecularMD is able to leverage the RecoverAll™ Total Nucleic Acid Isolation Kit for DNA/RNA dual extraction to maximize the amount of data that can be obtained from a minimal amount of tissue.

“This targeted panel approach reduces the amount of input material so that the amount of tumor tissue needed for TMB testing is minimized compared to other methods,” Spittle added.

During its early studies, MolecularMD also developed an alternative workflow and quality control method to address deamination errors in certain cases. The team found that samples of the poorest quality, which sometimes contain these errors, may overestimate TMB. The modified approach leverages duplicate sample runs and proprietary bioinformatics to filter out and reduce false positive variant calls.

Jin Li, Ph.D., and Executive Director of NGS Clinical Development at MolecularMD, explained: “The modified workflow accounts for poor quality DNA due to deamination during tissue fixation. We believe that a number of initial SNV calls in a subset of samples may be due to sample quality, leading to falsely elevated TMB scores.”

The Oncomine Tumor Mutation Load Assay is offered to MolecularMD’s clients who are engaged in translational research and clinical trials. Additional studies are underway to determine the clinical utility of TMB analysis for predicting patient response to checkpoint inhibitors.

“In addition to the validation of standardized panels and workflows, the development of tumor-specific TMB ranges and cut-off criteria are needed to drive precision medicine in immuno-oncology,” Dr. Spittle said.

“We are pleased that MolecularMD has adopted the Oncomine Tumor Mutation Load Assay to enable clinical research and clinical trials focused on immuno-oncology applications,” said Joydeep Goswami, President of Clinical Next-Generation Sequencing and Oncology at Thermo Fisher Scientific. “This is an important step toward standardizing a targeted NGS approach for TMB assessment and for moving precision medicine forward.”