Selpercatinib (LOXO-292)

Agent Description

Selpercatinib is an investigational selective RET inhibitor being studied for the treatment of RET fusion-positive cancers across tumor types and RET-mutated medullary thyroid cancer (MTC).

Mechanism of Action

Selpercatinib binds to the ATP-binding site of the RET kinase, preventing it from downstream signaling.

Classification

Selective RET inhibitor

Molecular Targets

RET

Monograph

Selpercatinib has Breakthrough Therapy Designation in three indications:

For the treatment of patients with metastatic RET-fusion positive NSCLC who require systemic therapy and have progressed following platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 therapy.
For the treatment of patients with RET-mutant MTC who require systemic therapy, have progressed following prior treatment and have no acceptable alternative treatment options.
For the treatment of patients with advanced RET fusion-positive thyroid cancer who require systemic therapy, have progressed following prior treatment and have no acceptable alternative treatment options.

The results of a phase 1/2 study of selpercatinib in patients with advanced solid tumors, RET fusion-positive solid tumors, and MTC have been recently presented.

A randomized, phase 3 study in treatment-naïve RET fusion-positive NSCLC is being implemented to evaluate selpercatinib versus pemetrexed with a platinum agent with or without pembrolizumab.

A randomized, phase 3 study is being designed to evaluate selpercatinib versus cabozantinib or vandetanib (investigators choice) in kinase inhibitor-naïve RET-mutant MTC.

Studies of Interest

Studies evaluating RET-fusion positive NSCLC in first line setting
Studies evaluating RET-mutant MTC in first line setting
Studies evaluating pediatric patients

Concepts that would not be supported are those that compete against ongoing or future Loxo Oncology or Lilly-sponsored studies.

Information collaborator would like included in investigator proposals

N/A