FDA Grants Traditional Approval to Tepmetko for Metastatic Non–Small Cell Lung Cancer

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EMD Serono, Merck KGaA’s biopharmaceutical business, scored a traditional approval for Tepmetko (tepotinib) to treat adults with metastatic non–small cell lung cancer (NSCLC) harboring MET exon 14 skipping alterations.¹ The oral MET inhibitor was developed to inhibit oncogenic MET receptor signaling that is caused by alterations to the MET gene, including METex14 skipping alterations and MET amplifications.

The FDA previously granted accelerated approval to Tepmetko for metastatic NSCLC based on findings from the single-arm, open-label, multicenter, non-randomized, multicohort Phase II VISION trial (NCT02864992). Investigators enrolled patients with advanced or metastatic NSCLC harboring MET exon 14 skipping alterations who were negative for EGFR wild-type disease and ALK aberrations. Patients were administered 450 mg of Tepmetko once daily until disease progression or intolerable toxicity.²

The results showed that Tepmetko produced an objective response rate (ORR) of 43% in 69 treatment-naive patients per blinded independent review committee and RECIST v1.1 criteria.³ Median duration of response (DOR) was 10.8 months, whereas in 83 patients who received prior treatment, ORR was 43% and median DOR was 11.1 months. The regulatory action to convert the accelerated approval to a traditional approval was based on findings from an additional 161 patients after 28 months of added follow-up time for DOR.¹

Among 164 evaluable patients who did not receive prior treatment, Tepmetko produced an ORR of 57%, with 40% of responders continuing to respond to treatment for 12 months or longer. In 149 evaluable patients who were previously treated, ORR was 45%, with 36% of responders achieving a DOR of at least 12 months.

In terms of safety, among 255 patients administered Tepmetko in the VISION trial, 45% experienced serious adverse events (AEs), with three fatal AEs in the form of pneumonitis, hepatic failure, and dyspnea from fluid overload. Further, 44% of patients required dose interruptions because of an AE, 30% required dose reductions, and 20% of patients discontinued treatment because of toxicity.

The most common AEs reported in at least 10% of patients included edema (all grades, 70%; grades 3 to 4, 9%), fatigue (27%; 1.6%), nausea (27%; 0.8%), diarrhea (26%; 0.4%), abdominal pain (16%; 0.8%), constipation (16%; 0%), vomiting (13%; 1.2%), musculoskeletal pain (24%; 2.4%), dyspnea (20%; 2%), cough (15%; 0.4%), pleural effusion (13%; 5%), reduced appetite (16%; 1.2%), and pneumonia (11%; 3.9%).

The most common laboratory abnormalities reported by 20% or more of patients administered Tepmetko that worsened from baseline were reduced albumin (grades 1 to 4, 76%; grades 3 to 4, 9%), reduced sodium (31%; 8%), reduced lymphocytes (48%; 11%), reduced hemoglobin (27%; 2%), and reduced leukocytes (23%; 0.8%).

Other common laboratory abnormalities included elevated creatinine (grades 1 to 4, 55%; grades 3 to 4, 0.4%), elevated alkaline phosphatase (50%; 1.6%), elevated alanine aminotransferase (44%; 4.1%), elevated aspartate aminotransferase (35%; 2.5%), elevated potassium (25%; 1.6%), elevated gamma-glutamyltransferase (24%; 5%), and elevated amylase (23%; 4.6%).

References

1. FDA approves tepotinib for metastatic non-small cell lung cancer. FDA. February 16, 2024. Accessed February 15, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-tepotinib-metastatic-non-small-cell-lung-cancer

2. FDA grants accelerated approval to tepotinib for metastatic non-small cell lung cancer. News release. FDA. February 3, 2021. Accessed February 16, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tepotinib-metastatic-non-small-cell-lung-cancer

3. Tepmetko. Prescribing information. EMD Serono; 2024. Accessed February 16, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/214096s001s002lbl.pdf