Pralsetinib

Pralsetinib, like the previously authorized selpercatinib, is a kinase inhibitor that exhibits heightened selectivity for RET tyrosine kinase receptors (RTKs) compared to other RTK categories. Enhanced expression of the RET (Rearranged during Transfection) oncogene is a defining characteristic of numerous cancers, including non-small cell lung cancer. While multikinase inhibitors, such as cabozantinib, ponatinib, sorafenib, sunitinib, and vandetanib, have demonstrated effectiveness in RET-driven cancers, their lack of specificity is often associated with significant toxicity. Pralsetinib (BLU-667) and selpercatinib (LOXO-292) are the initial generation of specific RET RTK inhibitors developed for treating RET-driven cancers.

Despite the ongoing Phase 1/2 pralsetinib trial, known as ARROW (NCT03037385), pralsetinib received accelerated FDA approval on September 4, 2020, for managing metastatic RET-fusion-positive non-small cell lung cancer. The product is currently available in the market under the brand name GAVRETO™.