Selpercatinib (Retevmo®): A Comprehensive Monograph on a First-in-Class Selective RET Inhibitor

Executive Summary

Selpercatinib, marketed under the brand names Retevmo® and Retsevmo®, is a first-in-class, orally bioavailable, small-molecule inhibitor of the Rearranged during Transfection (RET) receptor tyrosine kinase. It represents a landmark achievement in precision oncology, having been specifically designed for high potency and selectivity against cancers driven by RET gene alterations, including activating point mutations and oncogenic fusions. The development and approval of selpercatinib have fundamentally transformed the treatment landscape for patient populations with previously limited therapeutic options.

Clinical validation for selpercatinib is anchored in the results of the pivotal, multicenter Phase 1/2 LIBRETTO-001 trial, which demonstrated unprecedented and durable clinical activity across multiple tumor types. In its approved indications, selpercatinib has produced high objective response rates (ORR) and prolonged durations of response (DoR) and progression-free survival (PFS). Key approved indications include RET fusion-positive non-small cell lung cancer (NSCLC), both in treatment-naïve and previously treated settings; advanced RET-mutant medullary thyroid cancer (MTC); advanced RET fusion-positive thyroid cancer; and a tumor-agnostic indication for advanced RET fusion-positive solid tumors that have progressed on prior therapy.