FDA Approves FoundationOne CDx as Companion Diagnostic for Tepotinib in MET Exon 14-Positive NSCLC
Key Insights
The FDA has approved FoundationOne CDx as a companion diagnostic for tepotinib (TEPMETKO) to identify patients with metastatic non-small cell lung cancer harboring MET exon 14 (search) skipping alterations.
This approval marks Foundation Medicine's first real-world data-powered companion diagnostic approval, leveraging curated clinical-genomic datasets to supplement clinical trial evidence.
Combined with the previously approved FoundationOne Liquid CDx, clinicians now have both tissue- and blood-based FDA-approved testing options for identifying patients eligible for tepotinib treatment.
The U.S. Food and Drug Administration has approved FoundationOne CDx as a companion diagnostic for tepotinib (TEPMETKO) to identify patients with metastatic non-small cell lung cancer harboring MET exon 14 (search) skipping alterations. This approval expands testing options for patients with METex14-positive NSCLC by allowing Foundation Medicine's tissue-based comprehensive genomic profiling test to support treatment selection for tepotinib.
The decision follows the earlier FDA approval of FoundationOne Liquid CDx as a blood-based companion diagnostic for TEPMETKO in November 2024. Together, the two approvals mean that both tissue and liquid biopsy approaches from Foundation Medicine can now be used to identify patients who may be eligible for tepotinib treatment when MET exon 14 (search) skipping alterations are detected.
Clinical Significance of MET Exon 14 Testing
MET exon 14 (search) skipping alterations are found in approximately 3-4% of NSCLC cases and are associated with advanced disease and poor prognosis. For patients with metastatic NSCLC, timely and accurate molecular testing is essential because METex14 is a targetable alteration with an approved treatment option.
TEPMETKO received accelerated FDA approval in February 2021 and traditional FDA approval in February 2024 for adults with metastatic NSCLC harboring MET exon 14 (search) skipping alterations. The new companion diagnostic approval strengthens the testing pathway by adding a tissue-based FDA-approved option to identify eligible patients.
Comprehensive Testing Platform
FoundationOne CDx is a next-generation sequencing-based tissue test that analyzes 324 cancer-related genes using DNA from formalin-fixed, paraffin-embedded tumor tissue. It detects substitutions, insertions and deletions, copy number alterations, selected rearrangements, and genomic signatures including microsatellite instability and tumor mutational burden.
FoundationOne Liquid CDx, the company's blood-based comprehensive genomic profiling test, had already received FDA approval as a companion diagnostic for TEPMETKO. This is particularly relevant when tumor tissue is limited, unavailable, or difficult to obtain. However, a negative liquid biopsy result does not rule out the presence of an alteration, and tissue testing may still be needed when feasible.
Real-World Data Innovation
A notable aspect of this announcement is that it represents Foundation Medicine's first real-world data-powered companion diagnostic approval. According to the company, the approval leveraged its real-world data-powered CDx offering, which supports diagnostic label expansion by supplementing clinical trial evidence with curated real-world evidence and regulatory support.
The company highlighted the role of the Flatiron Health (search)–Foundation Medicine Clinico-Genomic Database, which includes data from more than 150,000 patients. This resource can help generate regulatory-grade real-world data cohorts, potentially reducing the need for additional patient enrollment while maintaining evidence standards for companion diagnostic projects.
"This approval reinforces the importance of having diverse, high-quality testing options to support healthcare providers in making informed treatment decisions for their patients, regardless of available sample type," said Todd Druley, MD, PhD, chief medical officer at Foundation Medicine. "This milestone also highlights our commitment to finding novel avenues to enable expanded patient access. In the many cases where samples are depleted and the time needed for a new trial is unfeasible, rigorous, regulatory-aligned real-world evidence can complement pre-existing clinical trial data to help expand the available options for patients."
Tepotinib Efficacy Data
The FDA originally approved tepotinib as a treatment for patients with NSCLC harboring MET exon 14 (search) skipping alterations in February 2024. Supporting data for the approval came from the phase 2 VISION trial, which evaluated the agent among 313 patients with MET-altered NSCLC.
Data demonstrated an overall response rate of 57% (95% CI, 49%-65%) among 164 patients who received no prior therapy, with 40% of responders experiencing a response duration of at least 12 months. Additionally, the overall response rate was 45% (95% CI, 37%-53%) among 149 patients with previously treated disease, which included 36% of responders having a sustained response for at least 12 months.
The most common toxicities included edema, nausea, fatigue, musculoskeletal pain, diarrhea, dyspnea, decreased appetite, and rash.
Impact on Clinical Practice
For clinicians treating metastatic NSCLC, this approval reinforces the importance of comprehensive genomic profiling at diagnosis and during treatment planning. MET exon 14 (search) skipping is uncommon but actionable, and missing this alteration can mean missing an approved targeted therapy option.
The availability of both tissue and liquid biopsy companion diagnostics may help improve patient identification across real-world clinical scenarios. Tissue testing remains important when adequate tumor material is available, while liquid biopsy can be useful when tissue is insufficient or when faster, less invasive testing is needed.
"Innovation in targeted therapies for lung cancer has helped pave the way for progress in precision medicine, but there is still much work needed to connect the right patients to the right therapies, and to find new options for patients. We're excited to see the value that regulatory-grade, real-world data can add to increase agility, while maintaining the highest standards for patient care," said Danielle Hicks, co-interim chief executive officer and chief patient officer at GO2 for Lung Cancer (search).