Expanding the Promise of Immunotherapy with Blood Tumor Mutational Burden (bTMB)

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A quick glance at the latest news coverage reveals the increasing pace of new treatment approvals and clinical advances in oncology, many of which are happening in one specific field: cancer immunotherapy.

Some of these advances are being matched by new biomarkers to help predict who is most likely to benefit from this emerging class of medicine. A new genomic biomarker, tumor mutational burden (TMB), has been shown to help predict patient response to checkpoint inhibitor immunotherapies across a range of tumor types, including lung, bladder and melanoma. With a single tissue sample, oncologists can use FoundationOne® to measure TMB, which has great potential to make a significant impact on the immunotherapy treatment landscape.

But being able to predict patient response isn’t just about matching patients with the right therapies. It’s also about expanding the potential benefit of precision medicine and cancer immunotherapy to patients for whom tissue biopsies are not feasible.

Introducing blood tumor mutational burden (bTMB)

A new, non-invasive assay from Foundation Medicine measures TMB in blood and has the potential to predict response to checkpoint inhibitor immunotherapy, expanding access to patients who simply cannot undergo surgery for a recent tissue biopsy because their disease burden is too great, or their health is too compromised.

At Foundation Medicine, we’re committed to leading the transformation in personalized cancer care by developing solutions that optimize the patient journey. This is accomplished by improving access to the right therapy and expanding personalized care options for patients with advanced cancer. Blood tumor mutational burden (bTMB) is the next step in our commitment to help re-define the treatment landscape for cancer immunotherapy. Using only a blood draw, bTMB can help identify more people likely to respond to immunotherapy, such as the estimated 1 in 3 patients with advanced lung cancer who don’t have access to a tissue biopsy.i This test can also help improve the identification of patients for immunotherapy clinical trials – potentially helping to accelerate the pace of new treatment development.

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bTMB as a non-invasive biomarker of immunotherapy response

We’re presenting two studies at this year’s European Society for Medical Oncology (ESMO) Annual Meeting which demonstrate the role bTMB could have in expanding precision medicine to more patients. In an analytic validation study, we show that this assay can determine bTMB with high precision and accuracy from as little as one percent tumor in the cell free DNA.

Because blood typically has a smaller amount of tumor DNA compared with a tumor tissue sample, blood-based genomic assays must be much more sensitive than those which use a tissue biopsy. Our new bTMB assay, like our circulating tumor DNA (ctDNA) genomic profiling assay FoundationACT, is designed and validated to be highly sensitive even at low tumor content.

In addition, a retrospective analysis from two clinical trials of the anti-PD-L1 immunotherapy atezolizumab showed that bTMB is associated with longer progression-free survival in people with previously-treated non-small cell lung cancer (NSCLC). These data represent the first evidence that a genomic biomarker measured in the blood could be used as a predictor of response to immunotherapy.

These data are particularly important for the lung cancer community where the disease can progress quickly and patients may not be able to safely undergo another tissue biopsy. Based on these promising new findings, bTMB will be integrated as a companion diagnostic assay in a new Phase 3 clinical trial which will investigate bTMB as a non-invasive biomarker of response to first-line immunotherapy in advanced NSCLC patients. Our vision and goal is that inclusion in clinical trials like these will validate the use of bTMB to help identify more patients likely to respond to immunotherapy treatment, regardless of the stage of their disease.

Pushing boundaries

We continue to be at the forefront of precision medicine. Blood-based testing to inform cancer treatment is evolving quickly, and bTMB could represent a new way to extend life-prolonging treatments to patients while simultaneously helping our biopharma partners design more effective clinical trials of novel immunotherapy treatments.

The results of these studies are being presented at ESMO 2017.

ESMO bTMB abstracts:

Abstract #1295O -- Blood-based biomarkers for cancer immunotherapy: Tumor mutational burden in blood (bTMB) is associated with improved atezolizumab (atezo) efficacy in 2L+ NSCLC (POPLAR and OAK); Sept 8, 4:00pm - 5:30pm, Madrid Auditorium.

Abstract #102P -- Analytic validation of a next generation sequencing assay to identify tumor mutational burden from blood (bTMB) to support investigation of an anti-PD-L1 agent, atezolizumab, in a first line non-small cell lung cancer trial (BFAST); Sept 11, 1:15pm - 2:15pm, Hall 8.

1 Kris et al. Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs. JAMA. 2014;311(19):1998-2006.