FDA News

FDA grants breakthrough therapy designation to tepotinib for lung cancer subset

The FDA granted breakthrough therapy designation to tepotinib for treatment of patients with metastatic non-small cell lung cancer who harbor MET exon 14 skipping alterations and progressed after platinum-based cancer therapy.

Approximately 3 % to 5% of patients with NSCLC have alterations of the MET signaling pathway, and MET exon 14 skipping alterations are associated with a particularly aggressive subtype of NSCLC. No therapies that specifically target MET alterations are approved in the United States.

Tepotinib ( MSC2156119; Merck / EMD Serono) is an investigational oral MET kinase inhibitor.

The FDA based the breakthrough therapy designation on data from the ongoing VISION study , which showed p reliminary clinical evidence of the agent’s effectiveness for patients with metastatic NSCLC who harbor MET exon 14 skipping alterations .

An interim analysis included 73 efficacy-evaluable patients with NSCLC with MET exon 14 skipping alterations identified by liquid biopsy or tissue biopsy testing.

In the liquid biopsy-identified group, results showed overall objective response rates of 50% by independent review committee assessment (median duration of response, 12.4 months) and 55.3% by investigator assessment (median duration, 17.1 months).

In the tissue biopsy-identified group, results showed ORRs of 45.1% by independent review committee assessment (median duration, 15.7 months) and 54.9% by investigator assessment (median duration, 14.3 months).

The majority of treatment-related adverse events were grade 1 or grade 2. Investigators observed no grade 4 or grade 5 treatment-related events.

The most common any-grade treatment-related adverse events reported among 87 safety- evaluable patients included peripheral edema (48.3%), nausea (23%) , diarrhea (20.7%) and increased blood creatinine (12.6%). Other any-grade events included increased lipase (4.6%), fatigue (3.4%) and vomiting (3.4%).

Four patients disc ontinued treatment due to treatment-related adverse events. These included two due to peripheral edema, one due to interstitial lung disease, and one due to nausea and diarrhea.

“ Tepotinib was associated with robust objective responses with durability that has not previously been seen in patients with metastatic NSCLC harboring MET exon 14 skipping alterations, selected by either tissue or liquid biopsy approaches,” Luciano Rossetti, MD, global head of research and development for the biopharma business of Merck KGaA in Darmstadt, Germany, said in a company-issued press release. “This breakthrough therapy designation further underscores the potential of tepotinib, and we aim to advance this program and deliver this medicine as quickly as possible to [patients with NSCLC] who may benefit.”

Tepotinib also is being evaluated in combination with the TKI osimertinib (Tagrisso, AstraZeneca) for patients with epidermal growth factor receptor-mutated, MET amplified, locally advanced or metastatic NSCLC who acquired resistance to prior EGFR TKI therapy.

The FDA granted breakthrough therapy designation to tepotinib for treatment of patients with metastatic non-small cell lung cancer who harbor MET exon 14 skipping alterations and progressed after platinum-based cancer therapy.

Approximately 3 % to 5% of patients with NSCLC have alterations of the MET signaling pathway, and MET exon 14 skipping alterations are associated with a particularly aggressive subtype of NSCLC. No therapies that specifically target MET alterations are approved in the United States.

Tepotinib ( MSC2156119; Merck / EMD Serono) is an investigational oral MET kinase inhibitor.

The FDA based the breakthrough therapy designation on data from the ongoing VISION study , which showed p reliminary clinical evidence of the agent’s effectiveness for patients with metastatic NSCLC who harbor MET exon 14 skipping alterations .

An interim analysis included 73 efficacy-evaluable patients with NSCLC with MET exon 14 skipping alterations identified by liquid biopsy or tissue biopsy testing.

In the liquid biopsy-identified group, results showed overall objective response rates of 50% by independent review committee assessment (median duration of response, 12.4 months) and 55.3% by investigator assessment (median duration, 17.1 months).

In the tissue biopsy-identified group, results showed ORRs of 45.1% by independent review committee assessment (median duration, 15.7 months) and 54.9% by investigator assessment (median duration, 14.3 months).

The majority of treatment-related adverse events were grade 1 or grade 2. Investigators observed no grade 4 or grade 5 treatment-related events.

The most common any-grade treatment-related adverse events reported among 87 safety- evaluable patients included peripheral edema (48.3%), nausea (23%) , diarrhea (20.7%) and increased blood creatinine (12.6%). Other any-grade events included increased lipase (4.6%), fatigue (3.4%) and vomiting (3.4%).

Four patients disc ontinued treatment due to treatment-related adverse events. These included two due to peripheral edema, one due to interstitial lung disease, and one due to nausea and diarrhea.

“ Tepotinib was associated with robust objective responses with durability that has not previously been seen in patients with metastatic NSCLC harboring MET exon 14 skipping alterations, selected by either tissue or liquid biopsy approaches,” Luciano Rossetti, MD, global head of research and development for the biopharma business of Merck KGaA in Darmstadt, Germany, said in a company-issued press release. “This breakthrough therapy designation further underscores the potential of tepotinib, and we aim to advance this program and deliver this medicine as quickly as possible to [patients with NSCLC] who may benefit.”

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Tepotinib also is being evaluated in combination with the TKI osimertinib (Tagrisso, AstraZeneca) for patients with epidermal growth factor receptor-mutated, MET amplified, locally advanced or metastatic NSCLC who acquired resistance to prior EGFR TKI therapy.