- A new blood-based biomarker test developed by Foundation Medicine, Inc. and Swiss pharma Roche AG could help identify which patients are more likely to respond to immunotherapy, particularly in cases where obtaining a standard tissue biopsy isn't possible.
- Unlike the current standard of testing patients for PD-L1 expression levels, Foundation's test aims to measure the number of mutations within a tumor genome in hopes of better predicting the patients that will see the most benefit from treatment.
- Foundation has been developing tissue-based measures of tumor mutational burden (TMB), but data presented by the companies at this weekend's meeting of the European Society for Medical Oncology (ESMO) is the first validation of whether TMB can be calculated from blood samples.
While immunotherapy has rapidly advanced clinical care in some cancers, many patients still don't see a benefit over standard treatment. Drugmakers like Roche, Merck & Co. and Bristol-Myers Squibb Co. have been struggling to puzzle out why and find better ways to determine likely responders.
PD-L1 expression, for all its value to date in helping filter appropriate patient populations, has limitations. Studies have shown higher levels are correlated with improved response rates. Yet, some patients with high scores still don't respond to treatment, and others with lower levels do. Additionally, there are no standard assays to test PD-L1 levels, making it difficult to compare across clinical trials.
Foundation hopes measuring TMB could help solve some of these problems and potentially replace, or at least be complementary to, testing for PD-L1 expression.
The data presented at ESMO on Friday helps to expand TMB's utility by demonstrating the approach can work using blood samples alone — important for patients whose age or disease progression makes obtaining tissue samples difficult.
"Foundation Medicine has previously shown that measuring tumor mutational burden from tissue samples can help reliably predict responses to immunotherapies," said Vincent Miller, Foundation Medicine's chief medical officer, in a statement. "However, a critical need exists for measuring TMB via a non-invasive solution for cancer patients for whom tissue is not available or when a biopsy is not feasible."
Together with Roche, Foundation prospectively analyzed the Swiss pharma's POPLAR and OAK studies of Tecentriq (atezolizumab) in second-line lung cancer. Looking first at POPLAR, Foundation filtered the trial's population by different "cut points" of TMB scores to establish thresholds associated with improved progression-free survival and overall survival.
Foundation then applied those same cut points to the OAK study population in a blinded way to test whether stratifying patients by TMB score could predict improved responses. Data showed a correlation between high TMB scores and longer progression-free survival, while preserving the overall survival benefit seen in the original OAK data.
Roche and Foundation now plan to prospectively validate blood-based TMB in two clinical studies. One, an umbrella trial known as BFAST, will evaluate either Tecentriq or Alecensa (alectinib) in first-line lung cancer, selecting the treatment drug based on the presence of a positive TMB score.
Foundation and Roche's evidence for blood-based TMB is so far only retrospective. Firmly establishing the predictive benefit of the test will require success in these types of prospective trials.
Furthermore, blood-based tests need to be much more sensitive than tissue-based assays, raising other concerns with properly validating the approach.
Yet the promise of greater convenience and superior patient identification has spurred pharmas to explore new frontiers like blood-based TMB testing.
"Pursuing next generation biomarker development is a critical component of our cancer immunotherapy strategy," said Sandra Horning, Roche's chief medical officer, in a statement.