FDA Approves FoundationOne®CDx as the First Companion Diagnostic to Identify Patients with Solid Tumors that are Tumor Mutational Burden-High and Appropriate for Treatment with Keytruda

CAMBRIDGE, Mass.–(BUSINESS WIRE)–Foundation Medicine, Inc., today announced that the U.S. Food and Drug Administration (FDA) approved FoundationOne®CDx as a companion diagnostic for KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, which was also approved under accelerated approval for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. FoundationOne CDx is the first and only FDA-approved companion diagnostic to measure TMB and help identify patients who may be appropriate for treatment with KEYTRUDA, regardless of solid tumor type.

TMB is a measure of the number of somatic mutations per coding region within a tumor’s genome.1 This genomic signature can help determine a patient’s likelihood to respond to immunotherapies. FoundationOne CDx, Foundation Medicine’s comprehensive genomic profiling (CGP) assay approved for all solid tumors, enables oncologists to identify TMB-H patients (≥ 10 mutations/megabase) with unresectable or metastatic solid tumors across all tumor types who could potentially benefit from KEYTRUDA.

“Immunotherapy is revolutionizing cancer treatment. Not only does this approval mean that clinicians will be able to identify more patients who could benefit from this treatment option, but it’s an important milestone in the shift toward making biomarker-driven, tumor agnostic therapies available to patients, which is possible through an FDA-approved companion diagnostic,” said Brian Alexander, M.D., M.P.H., chief medical officer at Foundation Medicine. “We’re proud to have been at the forefront of efforts to bring TMB from research into clinical practice in partnership with the oncology community. It’s exciting to see this breakthrough translate into advanced care for patients.”

FoundationOne CDx is the first FDA-approved CGP test that is clinically and analytically validated for all solid tumors and incorporates multiple companion diagnostic claims. It is currently approved as the companion diagnostic test for more than 20 therapies across multiple cancer types.

“This approval represents a paradigm shift toward biomarker-driven cancer treatment. It’s made possible in part by an unparalleled collaboration to better understand how TMB levels are measured and reported,” said Jeff Allen, President and CEO of Friends of Cancer Research. “TMB provides an additional tool to inform clinical care, especially for cancer patients previously ineligible for immunotherapy based on existing biomarkers.”

Merck also announced today that the FDA approved its supplemental Biologics License Application (sBLA) for KEYTRUDA, for adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. The accelerated approval was based on a prospectively planned and retrospective analysis of the KEYNOTE-158 open-label trial, which used a clinical trial assay (CTA) based on FoundationOne CDx to determine TMB status in patients’ tumor tissue. The results showed that patients with TMB-H in solid tumors (≥ 10 mutations/megabase) who were treated with KEYTRUDA had a higher overall response rate (29%) compared to patients with TMB <10 mut/Mb (6%).2

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA is now approved for two pan-tumor indications. In 2017, KEYTRUDA was granted FDA approval as the first cancer treatment based on a genomic signature, regardless of cancer type, in microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors. More information about KEYTRUDA can be found at www.keytruda.com.

About FoundationOne CDx

FoundationOne CDx is a next-generation sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed paraffin embedded (FFPE) tumor tissue specimens. FoundationOne CDx is for prescription use only and is intended as a companion diagnostic to identify patients who may benefit from treatment with certain targeted therapies in accordance with their approved therapeutic product labeling. Additionally, FoundationOne CDx is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology for patients with solid malignant neoplasms. Use of the test 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 a full list of targeted therapies for which FoundationOne CDx is indicated as a companion diagnostic, please visit http://www.F1CDxLabel.com.

About TMB

Tumor mutational burden (TMB) is a measure of the total number of mutations per coding area of a tumor genome.3 TMB is an additional genomic signature, similar to a biomarker, that can help identify more candidates likely to benefit from immunotherapy across a range of tumor types. Levels are measured by the number of non-inherited mutations occurring per megabase (1 million DNA base pairs) of the tumor genome.4 TMB-H tumors may be more likely to respond to certain immunotherapies because their high number of mutations make them easier for the immune system to identify. Higher TMB levels are correlated with higher levels of neoantigens, which help the immune system recognize and attack cancer cells.5 TMB can be measured with both tissue and blood-based comprehensive genomic tests.

About Foundation Medicine

Foundation Medicine is a molecular information company dedicated to a transformation in cancer care in which treatment is informed by a deep understanding of the genomic changes that contribute to each patient’s unique cancer. The company offers a full suite of comprehensive genomic profiling assays to identify the molecular alterations in a patient’s cancer and match them with relevant targeted therapies, immunotherapies and clinical trials. Foundation Medicine’s molecular information platform aims to improve day-to-day care for patients by serving the needs of clinicians, academic researchers and drug developers to help advance the science of molecular medicine in cancer. For more information, please visit www.FoundationMedicine.com or follow Foundation Medicine on Twitter (@FoundationATCG).

Foundation Medicine® and FoundationOne® are registered trademarks of Foundation Medicine, Inc.

KEYTRUDA® is a registered trademark of Merck.

Source: Foundation Medicine

1 NCI Cancer Dictionary. Tumor Mutational Burden. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/795825. Accessed March 5, 2020.
2 Marabelle et al. Annals of Oncology (2019) 30 (suppl_5): v475-v532. 10.1093/annonc/mdz253)
3 NCI Cancer Dictionary. Tumor Mutational Burden. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/795825. Accessed March 5, 2020.
4 NCI Cancer Dictionary. Tumor Mutational Burden. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/795825. Accessed March 5, 2020.
5 NCI Cancer Dictionary. Tumor Mutational Burden. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/795825. Accessed March 5, 2020.

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