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Several TRK inhibitors are in clinical development or have been licensed in some countries. These agents differ in stage of development, characteristics, and mode of action, as well as whether they address acquired resistance to TRK protein inhibition. 

The first-generation TRK inhibitors, larotrectinib and entrectinib, were granted landmark, tumour-agnostic regulatory approval after showing rapid and durable responses in patients with locally advanced or metastatic disease. Like other kinase inhibitors, acquired resistance to these first-generation of TRK inhibitors can eventually occur. Hence, a second-generation of agents designed to address target-mediated resistance has entered clinical development.

Find out more about acquired resistance to TRK protein inhibition

First Generation TRK Inhibitors: Larotrectinib, Entrectinib

Second Generation TRK Inhibitors: Repotrectinib, Taletrectinib

Other multikinase inhibitors with significant anti-TRK activity that are in clinical development are shown here.

Click on the links below to find out more about first-generation and second-generation TRK-selective inhibitors that are either licensed or under development.

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