The FDA ( US Food and Drug Administration ) has approved Tepmetko ( Tepotinib ) for the treatment of adult patients with metastatic non-small cell lung cancer ( NSCLC ) harboring mesenchymal-epithelial transition ( MET ) exon 14 skipping alterations ( METex14 ).
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
The approval is based on results from the pivotal phase II VISION study evaluating Tepotinib as monotherapy in patients with advanced NSCLC with METex14 skipping alterations.
Tepmetko is the first and only FDA approved MET inhibitor that offers once-daily oral dosing and is administered as two 225 mg tablets ( 450 mg ).
Patients with metastatic NSCLC should be selected for treatment with Tepmetko based on the presence of MET exon 14 skipping alterations.
VISION is an ongoing pivotal phase II, multicenter, multi-cohort, single-arm, non-randomized, open-label study investigating Tepotinib as monotherapy in 152 patients with a median age of 73 years with advanced or metastatic non-small cell lung cancer with MET exon 14 skipping alterations.
Eligible patients were required to have advanced or metastatic NSCLC harboring METex14 skipping alterations, epidermal growth factor receptor ( EGFR ) wild-type and anaplastic lymphoma kinase ( ALK ) negative status, at least one measurable lesion as defined by RECIST version 1.1, and ECOG Performance Status of 0 to 1.
Patients received Tepmetko 450 mg once daily until disease progression or unacceptable toxicity.
The major efficacy outcome measure is overall response rate ( ORR ) according to RECIST version 1.1 as assessed by a blinded independent review committee ( BIRC ). An additional efficacy outcome measure was duration of response ( DOR ) by BIRC.
Patients with symptomatic central nervous system ( CNS ) metastases, clinically significant uncontrolled cardiac disease, or who received treatment with any MET or hepatocyte growth factor ( HGF ) inhibitor were not eligible for the study.
Tepmetko has demonstrated an overall response rate of 43% ( 95% CI, 32–56 ) in treatment-naïve patients ( n=69 ) and 43% ( 95% CI, 33-55 ) in previously treated patients ( n=83 ).
Median duration of response was 10.8 months ( 95% CI, 6.9-NE ) and 11.1 months ( 95% CI, 9.5-18.5 ) among treatment-naïve and previously treated patients, respectively.
Duration of response of six months or more occurred among 67% of treatment-naïve patients and 75% of previously treated patients, and duration of response of nine months or more occurred among 30% of treatment-naïve patients and 50% of previously treated patients.
The safety population included 255 patients with NSCLC positive for METex14 skipping alterations, who received Tepmetko in the VISION study.
Fatal adverse reactions occurred in one patient ( 0.4% ) due to pneumonitis, one patient ( 0.4% ) due to hepatic failure, and one patient ( 0.4% ) due to dyspnea from fluid overload.
Serious adverse reactions occurred in 45% of patients who received Tepmetko. Serious adverse reactions occurring in more than 2% of patients included pleural effusion ( 7% ), pneumonia ( 5% ), edema ( 3.9% ), dyspnea ( 3.9% ), general health deterioration ( 3.5% ), pulmonary embolism ( 2% ), and musculoskeletal pain ( 2% ).
The most common adverse reactions ( 20% or more ) in patients who received Tepmetko were edema, fatigue, nausea, diarrhea, musculoskeletal pain, and dyspnea.
With 2 million cases diagnosed annually, lung cancer ( including trachea, bronchus and lung ) is the most common type of cancer worldwide and the leading cause of cancer-related death, with 1.9 million mortality cases worldwide each year.
In the US in 2020, there were an estimated 228,820 new cases of lung cancer and more than 135,000 deaths from lung cancer.
Alterations of the MET signaling pathway, including MET exon 14 skipping alterations, are estimated to occur in 3% to 4% of non-small cell lung cancer cases. ( Xagena )
Source: Merck KGaA, 2021