FDA Approves Companion Diagnostic for Tepotinib in mNSCLC Harboring MET Exon 14 Skipping Alterations

FDA

The FDA has approved the FoundationOne Liquid CDx for use as a companion diagnostic to identify patients with metastatic non–small cell lung cancer (mNSCLC) harboring MET exon 14 skipping alterations who may be eligible for treatment with tepotinib (Tepmetko).¹

On February 15, 2024, the FDA granted regular approval to tepotinib for the treatment of adult patients with mNSCLC harboring MET exon 14 skipping alterations.² This regulatory decision followed the February 2021 accelerated approval of the agent for this indication.³

“Access to a high-quality liquid biopsy, like FoundationOne Liquid CDx, can help unlock the power of precision medicine for more patients with NSCLC,” Mia Levy, MD, PhD, chief medical officer at Foundation Medicine, stated in a news release.¹ “We’re proud that our liquid biopsy is the first companion diagnostic approved in the United States for [tepotinib] as it will help identify more patients with MET exon 14 skipping alterations who may be appropriate for targeted treatment.”

Both the accelerated and regular approvals of tepotinib were supported by findings from the phase 2 VISION trial (NCT02864992).² In total, 313 patients with mNSCLC harboring MET exon 14 skipping alterations received tepotinib at the recommended dose of 450 mg once daily until unacceptable toxicity or disease progression. The primary efficacy end points were overall response rate (ORR) and duration of response (DOR). Of 164 previously untreated patients, the ORR was 57% (95% CI, 49%-65%), and 40% of responders had a DOR of at least 12 months. Of 149 previously treated patients, the ORR was 45% (95% CI, 37%-53%), and 36% of responders had a DOR of at least 12 months.

Further long-term efficacy findings showed that the median progression-free survival (PFS) in the treatment-naive cohort was 12.6 months (95% CI, 9.7-17.7); the 12- and 24-month PFS rates were 52% (95% CI, 43.0%-60.0%) and 38% (95% CI, 29.0%-47.0%), respectively.⁴ The median PFS in the previously treated cohort was 15.9 months (95% CI, 11.0-49.7); the respective 12- and 24-month PFS rates were 59% (95% CI, 48.0%-69.0%) and 42% (95% CI, 30.0%-53.0%).

In the treatment-naive and previously treated populations, the median overall survival was 21.3 months (95% CI, 14.2-25.9) and 29.7 months (18.8-not evaluable), respectively.

EQ-5D-5L Visual Analogue Scale and EORTC Core Quality of Life (QOL) Global Health Status questionnaire responses demonstrated stability in overall health-related QOL outcomes over time. EORTC QLQ-LC13 symptom scores for dyspnea and chest pain remained stable, and these scores for cough had a clinically meaningful improvement.

A pooled safety population included 448 patients with solid tumors enrolled across 5 open-label, single-arm trials in which they received tepotinib monotherapy at the recommended dose.⁵ This population included 255 patients from the VISION trial. In the VISION safety population, 45% of patients had serious adverse effects (AEs), the most common being pleural effusion (7%), pneumonia (5%), dyspnea (3.9%), edema (3.9%), general health deterioration (3.5%), musculoskeletal pain (2%), and pulmonary embolism (2%). One patient each died due to pneumonitis, hepatic failure, and dyspnea from fluid overload. The most common AEs included edema, nausea, fatigue, musculoskeletal pain, diarrhea, dyspnea, decreased appetite, and rash.

“Targeted therapies have led a revolution to how lung cancer is treated,” Laurie Ambrose, president and chief executive officer of GO2 for Lung Cancer, added in the news release.¹ “Biomarker testing plays a crucial part in getting these treatments into the hands of patients. We’re excited to see that patients with advanced NSCLC have more access to treatment options because of noninvasive liquid biopsies.”

References

1. U.S. Food and Drug Administration approves FoundationOneLiquid CDx as a companion diagnostic for Tepmetko (tepotinib) to identify patients with MET exon 14 skipping alterations in non-small cell lung cancer. News release. Foundation Medicine. November 18, 2024. Accessed November 18, 2024. https://www.foundationmedicine.com/press-release/fda-approval-foundationone-liquid-cdx-tepmetko
2. FDA approves tepotinib for metastatic non-small cell lung cancer. FDA. February 15, 2024. Accessed November 18, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tepotinib-metastatic-non-small-cell-lung-cancer
3. FDA grants accelerated approval to tepotinib for metastatic non-small cell lung cancer. FDA. February 3, 2021. Accessed November 18, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tepotinib-metastatic-non-small-cell-lung-cancer
4. Paik PK, Garassino MC, Le X, et al. Long-term outcomes of tepotinib in patients with MET exon 14 skipping NSCLC from the VISION study. J Clin Oncol. 2023;41(suppl 16):9060. doi:10.1200/JCO.2023.41.16_suppl.9060
5. Tepmetko. Prescribing information. EMD Serono; 2023. Accessed November 18, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/214096s001s002lbl.pdf