FoundationOne CDx Approved for Detecting TMB-H Solid Tumors Eligible for Pembrolizumab

FoundationOne CDx has been approved by the FDA as a companion diagnostic for pembrolizumab to identify patients with tumor mutational burden–high solid tumors who would benefit from this therapy.

The FDA has approved the use of FoundationOne CDx as a companion diagnostic for pembrolizumab (Keytruda) to identify patients with tumor mutational burden–high (TMB-H) solid tumors who would benefit from treatment with the immunotherapy.1 

Pembrolizumab was recently granted an accelerated approval by the FDA for the treatment of adult and pediatric patients with unresectable or metastatic, TMB-high (defined as ≥10 mutations/megabase) solid tumors, as determined by an FDA-approved test, who have progressed following prior therapy and have no satisfactory alternative treatment options.2

FoundationOne CDx is the only companion diagnostic that is FDA approved to measure TMB and to help identify patients who would be eligible for treatment with pembrolizumab, regardless of their tumor type, according to a press release from Foundation Medicine.1 

“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,” Brian Alexander, MD, MPH, chief medical officer at Foundation Medicine, said in the statement. “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 a next-generation sequencing–based in vitro diagnostic for detection of substitutions, indels, and copy number alterations across 324 genes and select gene rearrangements. The comprehensive genomic profiling assay also detects genomic signatures, such as microsatellite instability and TMB through DNA taken from formalin-fixed paraffin embedded tumor tissue samples. 

The assay is clinically and analytically validated for use across all solid tumors and is approved as a companion diagnostic for more than 20 treatments with multiple indications.

For the new pembrolizumab indication, the FoundationOne CDx assay can recognize TMB across all tumor types for the identification of patients with tumor TMB of at least 10 mutations/megabase.

The FDA approval for the tumor-agnostic indication for pembrolizumab was based off an analysis of 10 cohorts from the ongoing phase 2 KEYNOTE-158 trial that included 102 patients with previously treated unresectable or metastatic solid tumors and high TMB being treated with the PD-1 inhibitor. In the study, patients’ TMB status was assessed using a clinical trial assay based on FoundationOne CDx.2 

Responses were seen in 29% of patients with complete responses in 4% and partial responses in 25%. Comparatively, patients with TMB of less than 10 mutations/megabase had an overall response rate of 6%. The median duration of response was not yet reached but 57% of patients had responses ongoing for more than 1 year, and 50% for more than 2 years. 


  1. FoundationOne®CDx Receives FDA Approval as the First Companion Diagnostic to Identify Advanced Cancer Patients with Solid Tumors that are Tumor Mutational Burden-High (TMB-H) and Appropriate for Immunotherapy Treatment with KEYTRUDA® (pembrolizumab). News release. Foundation Medicine. June 17, 2020. Accessed June 17, 2020.
  2. FDA approves pembrolizumab for adults and children with TMB-H solid tumors. News release. FDA. June 17, 2020. Accessed June 17, 2020.