Immunotherapy Biomarkers

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Overview

We’re helping to uncover immunotherapy options for more patients

Cancer immunotherapies have the potential to treat cancer by harnessing the power of our own immune systems; however, not all cancer immunotherapies work for all patients. The ability to predict who is most likely to respond to cancer immunotherapies could save significant cost and precious time.

Help Identify More Eligible Patients

Tumor mutational burden (TMB) and microsatellite instability-high (MSI-H) are important genomic signatures to add to your standard PD-L1 testing because they may help identify more patients for whom immunotherapy could be an option.

All three populations, patients with elevated TMB, MSI-H, and positive PD-L1-status, have independently demonstrated improved response rate and prolonged progression-free survival on immunotherapy.1,2,3 However, there are groups of patients that test positive for only one of these three biomarkers.

Foundation Medicine Is Your Resource for Cancer Immunotherapy Information

Comprehensive genomic profiling with FoundationOne®CDx and FoundationOne®Liquid CDx, our FDA-approved tests, and FoundationOne®Heme, our laboratory developed test, can deliver insights into relevant cancer-related genes and measure other genomic signatures and clinical biomarkers, such as TMB, and MSI*, that may be associated with immunotherapy. We also offer PD-L1 testing as an optional add-on to a CGP test order.

Our tests can help physicians identify patients who may be more likely to benefit from immunotherapy by providing TMB, MSI, and PD-L1 testing from a single partner.

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*FoundationOne Liquid CDx reports on blood tumor mutational burden (bTMB) and MSI-H status as laboratory professional services which are not reviewed or approved by the FDA.4

Relevant Genomic Signatures

Tumor Mutational Burden (TMB)

TMB is a genomic signature that quantifies the frequency of somatic mutations in a patient’s tumor tissue or in circulating tumor DNA in blood. Elevated TMB correlates with higher neoantigen expression, which helps the immune system recognize tumors.5 It has been detected across numerous tumor types and has been associated with improved response rate and prolonged progression-free survival for patients on immunotherapy.6,7 TMB expands the population of patients who can be considered candidates for immunotherapy beyond standard PD-L1 testing.6,8

Currently FoundationOne CDx, FoundationOne Liquid CDx,* and FoundationOne Heme report TMB scores. As TMB is a quantitative genomic signature, current clinical trials are assessing therapeutic response at various cut-off levels in different tumor types.

*FoundationOne Liquid CDx reports on blood tumor mutational burden (bTMB) status as a laboratory professional service which is not reviewed or approved by the FDA.4

Relevant Genomic Signatures

Microsatellite Instability (MSI)

MSI is a genomic signature that is a signature of deficient mismatch repair (dMMR) which results in an abnormally high frequency of genetic mutations.9 MSI-high status correlates with higher neoantigen expression which helps the immune system recognize tumors.

Pembrolizumab is indicated for patients with MSI-H status across all solid tumor types when previous therapies have failed.10 High MSI levels have been detected in more than 20 types of solid tumors, thus underlining the importance of testing all patients for this key genomic signature.5,11

FoundationOne CDx, FoundationOne Liquid CDx,* and FoundationOne Heme provide MSI status on all reports.

*FoundationOne Liquid CDx reports on MSI-H status as a laboratory professional service which is not reviewed or approved by the FDA.4

Relevant Genomic Signatures

Programmed Death Ligand-1 (PD-L1)

PD-L1 is a protein biomarker that is strongly associated with immune system suppression.12 Positive PD-L1 immunohistochemistry (IHC) can indicate that a patient will be more likely to respond to immunotherapy. However, the variability of this biomarker highlights the need for additional tools to predict which patients may be candidates for immunotherapy.13

PD-L1 is available to order with FoundationOne CDx, FoundationOne Liquid CDx, and FoundationOne Heme on the same test requisition form. PD-L1 testing requires only four additional unstained slides. Scoring and clone utilization for PD-L1 testing is based on FDA-approved indications, learn more here.

Download Our IHC Specimen Instructions

By combining PD-L1, TMB, and MSI testing, you can be more confident that you are considering all viable immunotherapy treatment options for your patients.

Summary

Biomarker Summary

Foundation Medicine’s portfolio provides reliable and accurate measurements of TMB and MSI by comprehensive genomic profiling and PD-L1 expression by IHC. Leverage our tests to comprehensively help inform immunotherapy treatment options for your patients.

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Tumor Mutational Burden (TMB)

Definition

TMB is a genomic signature that quantifies the frequency of somatic mutations in a patient’s tumor or in circulating tumor DNA in blood. Increasing TMB correlates with increased numbers of neoantigens, which helps the immune system recognize tumors.

At Foundation Medicine

*FoundationOne Liquid CDx reports on blood tumor mutational burden (bTMB) as a laboratory professional service which is not reviewed or approved by the FDA.4

Reported As

  • Integer score
  • Therapies, trials and content will be reported using disease- and therapy-specific, score-based cutoffs based on existing clinical data, which may change over time as additional clinical data becomes available. For FoundationOne Liquid CDx, bTMB status will be reported in the professional services section of the report.

Microsatellite Instability (MSI)

Definition

MSI is a genomic signature that is a signature of deficient mismatch repair (dMMR) — which results in an abnormally high frequency of genetic mutations. MSI-high status correlates with higher neoantigen expression, which helps the immune system recognize tumors.

At Foundation Medicine

*FoundationOne Liquid CDx reports on blood tumor mutational burden (bTMB) as a laboratory professional service which is not reviewed or approved by the FDA.4

Reported As

FoundationOne CDx and FoundationOne Heme:

  • MSI-High
  • MSS (microsatellite stable)
  • CBD (cannot be determined)

FoundationOne Liquid CDx:

  • MSI-High
  • CBD (cannot be determined)

Programmed Death Ligand-1 (PD-L1)

Definition

PD-L1 is a protein biomarker whose expression is predictive of response to immunotherapy in multiple tumor types, as demonstrated in numerous clinical trials.

At Foundation Medicine

*Requires both blood and tissue specimens to proceed with FoundationOne Liquid CDx and PD-L1 testing

Reported As

The type of IHC score is dependent upon tumor type. Scoring and clone utilization is based on FDA-approved indications.

  • Tumor proportion score (TPS)
  • Tumor Cell Expression (%)
  • Combined positive score (CPS)
  • Tumor cell (TC) score (%)
  • Tumor-infiltrating immune cell (IC) score (%)

References

1Samstein RM. Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nature Genetics 2019;51:202-206.

2Stenger M. Pembrolizumab in MSI-H or dMMR Solid Tumors: ‘First Tissue/Site-Agnostic’ Approval by FDA. The ASCO Post [Internet]. 2018 Feb 10 [cited 2019 Jan 2]. Available from: www.ascopost.com/issues/february-10-2018/pembrolizumab-in-msi-h-or-dmmr-solid-tumors-first-tissuesite-agnostic-approval-by-fda/

3Center for Drug Evaluation and Research. (2019, February 06). Approved Drugs - Hematology/Oncology (Cancer) Approvals & Safety Notifications. Retrieved February 07, 2019, from www.fda.gov/Drugs/InformationOnDrugs/ApprovedDrugs/ucm279174.htm

4Gandara et al. Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab. Nat Med. 2018 Sep;24(9):1441-1448. doi: 10.1038/s41591-018-0134-3. Epub 2018 Aug 6.

5Chalmers ZR, et al. Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med. 2017;9:34. doi: 10.1186/s13073-017-0424-2.

6Goodman AM, et al. Tumor Mutational Burden as an Independent Predictor of Response to Immunotherapy in Diverse Cancers. Mol Cancer Ther. 2017;16(11):2598-608. doi: 10.1158/1535-7163.MCT-17-0386.

7Carbone D, et al. First-line Nivolumab in Stage IV or Recurrent Non-Small-Cell Lung Cancer. N Engl J Med. 2017;376:2415-26. doi: 10.1056/NEJMoa1613493.

8Internal Data on File.

9Kim TM, Laird PW, Park PJ. The Landscape of Microsatellite Instability in Colorectal and Endometrial Cancer Genomes. Cell. 2013;155(4):858-68. doi: 10.1016/j.cell.2013.10.015.

10Keytruda (pembrolizumab) [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp; 2014.

11Cortes-Ciriano I, et al. A molecular portrait of microsatellite instability across multiple cancers. Nature commun. 2017;8:15180.

12Xu-Monette ZY, et al. PD-1/PD-L1 Blockade: Have We Found the Key to Unleash the Antitumor Immune Response? Front Immunol. 2017;8:1597. doi:10.3389/fimmu.2017.01597.

13Kerr KM, Hirsch FR. Programmed Death Ligand-1 Immunohistochemistry: Friend Or Foe? Arch Pathol Lab Med. 2016;140:326–31. doi: 10.5858/arpa.2015-0522-SA.

FoundationOne Heme was developed and its performance characteristics determined by Foundation Medicine. It has not been cleared or approved by the U.S. Food and Drug Administration. For more information on this laboratory developed test (LDT) please see the Technical Specifications at foundationmedicine.com/f1h.

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Important Safety Information

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FoundationOne CDx and FoundationOne Liquid CDx

FoundationOne®CDx and FoundationOne®Liquid CDx are qualitative next-generation sequencing based in vitro diagnostic tests for advanced cancer patients with solid tumors and are for prescription use only. FoundationOne CDx utilizes FFPE tissue and analyzes 324 genes as well as genomic signatures. FoundationOne Liquid CDx analyzes 324 genes utilizing circulating cell-free DNA and is FDA-approved to report short variants in 311 genes. The tests are companion diagnostics to identify patients who may benefit from treatment with specific therapies in accordance with the therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the tests does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy for testing with FoundationOne CDx when archival tissue is not available which may pose a risk. When considering eligibility for ROZLYTREK® based on the detection of NTRK1/2/3 and ROS1 fusions, or for TEPMETKO® based on the detection of MET SNVs and indels that lead to MET exon 14 skipping, testing using plasma specimens is only appropriate for patients for whom tumor tissue is not available for testing. Patients who are tested with FoundationOne Liquid CDx and are negative for other companion diagnostic mutations should be reflexed to tumor tissue testing and mutation status confirmed using an FDA-approved tumor tissue test, if feasible. For the complete label, including companion diagnostic indications and important risk information, please visit www.F1CDxLabel.com and www.F1LCDxLabel.com.