Tepotinib/tepotinib

Generic name: Tepotinib

Trade name: Tepmetko

All names: Tepotinib hydrochloride tablets, Tepotinib, Tepotinib, Tepmetko

Adaptation Symptoms:

MET gene exon 14 skip mutation-positive non-small cell lung cancer with unresectable progression and recurrence

Usage and dosage:

Recommended dosage: 500 mg once a day, orally after meals. In phase 1 clinical trials, the maximum dose was ramped up to 1,400 mg once a day, which was still not the maximum tolerated dose.

Dose adjustment: If the dose needs to be reduced due to adverse reactions, the dose can be reduced to 250mg once a day. If still unable to tolerate 250 mg once daily, permanently discontinue treatment.

Adverse reactions:

Common adverse reactions (≥5%): peripheral edema (48.3%), nausea (23%), diarrhea (20 .7%), increased serum creatinine (12.6%), fatigue (9.2%), increased amylase (8%), increased ALT (6.9%), increased AST (5.7%) and hypoalbuminemia (5.7%).

Common grade 3 adverse reactions: peripheral edema (8%), increased amylase (2.3%), increased ALT (2.3%), diarrhea (1.1%), asthenia (1.1%), and increased AST (1.1%).

Other treatment-related adverse reactions: increased lipase (4.6%), fatigue (3.4%), vomiting (3.4%).

Contraindications:

Not clear

Precautions:

Interstitial lung disease/pneumonitis: In the VISON clinical trial, interstitial lung disease/pneumonitis occurred in 3.8% of patients. If a patient is found to have symptoms of interstitial lung disease/pneumonia, such as difficulty breathing, cough and fever, go to the hospital for examination and treatment in time.

Hepatotoxicity: In the VISON clinical trial, 13.1% of patients experienced elevated ALT, AST, γ-GTP, or ALP. Tepotinib is contraindicated in patients with severe hepatic impairment. Liver function needs to be checked before taking the medicine, and rechecked regularly while taking the medicine.

Peripheral edema: In the VISON clinical trial, adverse effects of fluid retention such as acroedema, hypoalbuminemia and pleural effusion were found. If you find any abnormalities such as significant weight gain or difficulty breathing while taking the medicine, go to the hospital for examination and treatment in time.

Embryo-fetal toxicity: Animal experiments show that Tepotinib has embryo-fetal toxicity. Patients and partners should use effective contraception while taking the drug and for one week after stopping the drug.

Nephrotoxicity: In the VISON clinical trial, adverse reactions such as increased serum creatinine (13.8%), renal insufficiency (2.3%) and acute kidney damage (1.5%) were found. Kidney function needs to be checked before taking the medicine and reviewed regularly while taking the medicine.

Storage:

Store at room temperature to avoid moisture. The validity period is 24 months.

Mechanism of action:

Tepotinib hydrochloride is a low molecular compound that inhibits mesenchymal epithelial transition factor (MET) and is a receptor tyrosine kinase. Tepotinib hydrochloride inhibits the phosphorylation of MET and is thought to exhibit tumor growth inhibition by inhibiting downstream signal transduction.

Safety and efficacy:

On February 3, 2021, EMD, a subsidiary of Merck KGaA of Germany Serono announced that the U.S. FDA has accelerated approval of the oral MET inhibitor Tepmetko (tepotinib) for the treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) carrying MET exon 14 (METex14) skipping mutations.

This approval is based on support from VISION's pivotal Phase 2 clinical trial. A total of 152 patients with advanced or metastatic NSCLC harboring METex14 skipping variants received Tepmetko as monotherapy. They do not carry EGFR or ALK gene mutations.

Trial results show that Tepmetko (tepotinib) achieved an overall response rate of 43% in both treatment-naive and treatment-experienced patients. The median duration of response (DOR) in treatment-naïve and treatment-experienced patients was 10.8 months (95% CI, 6.9-NE) and 11.1 months (95% CI, 9.5-18.5), respectively. 67% of treatment-naïve patients and 75% of treatment-experienced patients had a response duration of more than 6 months, and 30% of treatment-naive patients and 50% of treatment-experienced patients had a response duration of more than 9 months.