Selpercatinib resistance results

Selpercatinib is a highly selective RET inhibitor that blocks the adenosine triphosphate binding site of the RET receptor tyrosine kinase. Serpatinib has become a new and effective option for many patients due to its favorable properties in terms of target specificity, tolerability, and intracranial efficacy. In the phase 1/2 LIBRETTO-001 trial, a total of 105 patients with RET fusion NSCLC were treated with selpatinib with promising ORR and mDoR, and these patients had an mPFS of 16 months. Based on its anti-tumor efficacy and safety, serpatinib was approved by the FDA for RET fusion NSCLC on May 8, 2020.

Serpatinib is an intra-target kinase acquired resistance that evolves dynamically under selective pressure from kinase inhibitors, allowing sustained activation of the kinase in response to drug treatment. Includes gatekeeper mutations and solvent front mutations. It has been reported that resistance mechanisms to MKIs include the RET V804 M gatekeeper mutation and RET S904F. The selective RET inhibitor serpatinib induces pre-cleavage mutations.xa0

The original drug Serpatinib has not yet been launched in China, so it is not covered by medical insurance. Domestic patients cannot yet purchase this drug. Serpatinib marketed overseas The original drug has a US version and a European version. The price of the US version is about 150,000 yuan per box of 80mg*60 pills. The price of the European version of 80mg*56 pills per box is about 21,000 yuan (the price may fluctuate due to the exchange rate), which is expensive. There are also serpatinibgeneric drugs produced abroad. The specification produced by a Bangladesh pharmaceutical factory is 40mg*30 pills per box and the price is about 4,300 yuan (the price may fluctuate due to the exchange rate). The ingredients of the generic drugs are basically the same as those of the original drug.