On August 6, 2018 Foundation Medicine, reported the publication of the results of a large study demonstrating that its novel, investigational assay to measure blood tumor mutational burden (bTMB) can help predict response to the anti-PD-L1 immunotherapy, atezolizumab, (TECENTRIQ) in patients with previously treated non-small cell lung cancer (NSCLC) (Press release, Foundation Medicine, AUG 6, 2018, View Source [SID1234528460]). The study, published in the journal Nature Medicine, was the result of a collaboration between Foundation Medicine and Genentech, a member of the Roche Group, and demonstrates the potential of bTMB to expand precision oncology approaches for patients with advanced cancers, including metastatic lung cancer. In addition, these results show that bTMB may be an independent predictor of clinical benefit, regardless of PD-L1 expression as assessed by immunohistochemistry.

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"A significant proportion of patients with advanced lung cancer do not have adequate tissue for traditional biomarker testing. These study results represent an important advance for the liquid biopsy field and suggest that measuring TMB in the blood with our novel assay can help identify patients more likely to benefit from anti-PD-L1 immunotherapy," said Vincent Miller, M.D., chief medical officer at Foundation Medicine. "We look forward to further developing this assay through ongoing clinical trials and ultimately as a companion diagnostic to help oncologists make the most informed decisions possible, even when a tissue sample is not feasible."

In the study, clinical data for the novel bTMB assay was reported from a retrospective analysis of more than 1,000 samples from patients with previously treated, advanced NSCLC who participated in Genentech’s Phase II POPLAR and Phase III OAK clinical trials. The study used samples from the POPLAR trial to identify a range of bTMB thresholds that correlated with clinically meaningful outcomes, which were then confirmed using samples from the OAK study. Within the OAK study, patients with bTMB ≥ 16 total mutations (14 mut/Mb) showed significantly improved progression-free survival when treated with atezolizumab as compared to those patients with bTMB ≥ 16 total mutations (14 mut/Mb) treated with docetaxel chemotherapy (Hazard Ratio=0.65 [95% CI: 0.47, 0.92]; p=0.013). According to the study’s first author, David Gandara, M.D. of the UC Davis Comprehensive Cancer Center, "These are exciting times in lung cancer immunotherapy. Having a blood test that can identify those patients most likely to benefit would be a huge advantage for both physicians and patients. This publication is the first step toward what I anticipate will be full clinical application of this assay."

This bTMB assay is being prospectively evaluated in two Genentech studies: in the Phase III Blood First Assay Screening Trial (BFAST) as a companion diagnostic assay to validate bTMB as a non-invasive biomarker of response to first-line atezolizumab in advanced NSCLC patients, and in the single arm Phase II Blood First-Line Ready Screening Trial (B-F1RST) evaluating atezolizumab monotherapy in first-line NSCLC.

In April 2018, the U.S. Food and Drug Administration (FDA) granted a Breakthrough Device designation for Foundation Medicine’s new liquid biopsy assay, which will expand upon its current liquid biopsy assay to include genomic biomarkers for microsatellite instability (MSI) and bTMB. If approved, this test could be the first FDA-approved liquid biopsy assay to incorporate multiple companion diagnostics (CDx) and multiple biomarkers to inform the use of targeted oncology therapies, including immunotherapies.