US FDA approves tepotinib for treating metastatic NSCLC

US FDA approves tepotinib for treating metastatic NSCLC

The US FDA has recently approved tepotinib (Tepmetko) for the treatment of adults with metastatic non-small cell lung cancer (NSCLC) harbouring mesenchymal–epithelial transition exon 14 (METex14) skipping alterations.

Tepotinib is a once-daily, highly selective oral MET inhibitor that has shown promising clinical activity in patients with MET-driven tumours.

The approval is based on the pivotal phase 2 VISION study which is an ongoing multicentre 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 NSCLC that has METex14 skipping alterations.

Patients were negative for epidermal growth factor receptor wild type and anaplastic lymphoma kinase–negative, and had at least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1 and an ECOG (Eastern Cooperative Oncology Group) Performance Status of 0 to 1.

Patients with symptomatic central nervous system metastases, clinically significant uncontrolled cardiac disease, or who received treatment with any MET or hepatocyte growth factor inhibitor were ineligible for the study.

The patients received tepotinib 450 mg once daily until disease progression or unacceptable toxicity. The major efficacy outcome measure was overall response rate (ORR) according to response evaluation criteria in solid tumours (RECIST) version 1.1, as assessed by a blinded independent review committee. An additional efficacy outcome measure was duration of response (DOR).  DOR measured the length of time that a tumour continued to respond to treatment without cancer growing or spreading.

Tepotinib demonstrated an overall response rate of 43% (95% CI, 32%-56%) in treatment-naive patients (n=69).The median duration of response, or DoR, was 10.8 months and 11.1 months among treatment-naive and treatment-experienced patients, respectively. D DOR of six months or more occurred among 67% of treatment-naive patients and 75% of previously treated patients, and DOR of nine months or more occurred among 30% of treatment-naive patients and 50% of previously treated patients.

The researchers assessed safety in 255 patients who received tepotinib 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 tepotinib, including pleural effusion, pneumonia, oedema, dyspnea, general health deterioration, pulmonary embolism and musculoskeletal pain. The most common adverse reactions were oedema, fatigue, nausea, diarrhoea, musculoskeletal pain and dyspnea.