Clinical Trials

Date: 2018-08-06

Type of information: Publication of results in a medical journal


Announcement: publication of results in Nature Medicine

Company: Foundation Medicine (USA - MA) Roche (Switzerland)

Product: biomarker blood tumor mutational burden (bTMB)

Action mechanism: biomarker - genomic profile tests for cancer immunotherapies


Therapeutic area: Cancer - Oncology


Trial details:

Latest news:

  • • On August 6, 2018, Foundation Medicine announced 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). The study, published in 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 (Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab). In addition, these results show that bTMB may be an independent predictor of clinical benefit, regardless of PD-L1 expression as assessed by immunohistochemistry.
  • 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).
  • 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.
  • • On September 8, 2017,  Foundation Medicine announced presentations at the European Society for Medical Oncology (ESMO) Annual Meeting highlighting validation data for its novel assay to measure tumor mutational burden from blood (bTMB). These presentations will highlight retrospective data analysis from Roche/Genentech's Phase II POPLAR and Phase III OAK studies that enabled analytic and clinical validation for the bTMB assay. The studies demonstrate that high bTMB as measured by Foundation Medicine's assay is associated with response to atezolizumab in individuals with previously-treated non-small cell lung cancer (NSCLC), potentially offering a new option to expand personalized care options for patients with advanced cancer.
  • Based on these findings, Foundation Medicine also announced that its bTMB assay will be integrated as part of Roche/Genentech's prospective, randomized Phase III Blood First Assay Screening Trial (BFAST) as a companion diagnostic assay to investigate bTMB as a non-invasive biomarker of response to first-line atezolizumab in advanced NSCLC patients. In the studies presented at ESMO, Foundation Medicine's bTMB assay was analytically validated to determine TMB with high precision and accuracy from as little as one percent tumor content in a blood sample. The assay was used to retrospectively analyze a total of 794 plasma samples from the Phase II POPLAR and Phase III OAK clinical trials. The analysis showed that atezolizumab demonstrated a clear benefit for overall survival. Additionally, there was a correlation between patients with high bTMB in those studies and longer progression-free survival (PFS) when treated with atezolizumab. In addition, bTMB was not found to correlate with PD-L1 expression levels as measured by tissue-based immunohistochemistry, suggesting that bTMB, like tissue TMB, provides independent and critical predictive information in addition to the information furnished by PD-L1 testing.

Is general: Yes