Selpercatinib Approved by FDA for Solid Tumor Treatment

By Emily Menendez - Last Updated: December 22, 2022

The FDA has approved the cancer drug selpercatinib for two new solid tumor indications: locally advanced or metastatic rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), and for solid tumors with RET gene fusion mutations.  

What are RET Fusions? 

RET fusions are oncogenic drivers that are found in 1 to 2% of all diagnosed cases of NSCLC. In RET fusions, a piece of DNA joins another gene to create a fusion that then causes uncontrollable cell growth. RET fusions are estimated to account for a global lung cancer burden of over 10,000 new cases every year and more often occurs in younger NSCLC patients who have little to no history of smoking. Selpercatinib has been found to have nanomolar potency against diverse RET alterations, and it can penetrate the central nervous system to provide antitumor activity in the brain. 

The LIBRETTO-001 Trial 

Early findings from the phase 1/2 LIBRETTO-001 trial on the effectiveness of selpercatinib helped to gain the drug approval. The trial took place from May 2017 to December 2018, and 105 patients with advanced RET fusion-positive NSCLC were enrolled. The patients had previously received at least platinum-based chemotherapy as a prior treatment option. Selpercatinib was given continuously to patients in an oral capsule or liquid form in 28-day cycles and stopped if disease progression, death, unacceptable toxic effects, or withdrawal of consent occurred. 

Patients in the phase 1 section of the trial were given doses from 20 mg once daily to 240 mg twice daily. Patients in the phase 2 section were given the typical recommended dose of 160 mg twice daily. The primary treatment endpoint was complete or partial response, and secondary endpoints were an objective intracranial response, progression-free survival, duration of response, and safety. 

Promising Trial Findings for Selpercatinib 

An objective response was found in 64% of the patients. Out of these patients, 2% saw complete response, while 62% had a partial response. Stable disease was still found in 29% of the patients, 4% had progressive disease, and 4% could not be evaluated. At a one-year follow-up, 66% of all patients were found to be progression-free. The median progression-free survival rate was 16.5 months. Out of the 105 patients, 11 were found to have measurable lesions according to the Response Evaluation Criteria in Solid Tumors (RECIST). Out of these 11 patients, 91% of them had an objective intracranial response, with three complete response, seven partial responses, and one stable disease. The median central nervous system response duration was 10.1 months. 

The frequency of intracranial response to selpercatinib was particularly important considering the high lifetime risk of brain metastases in patients with RET fusion-positive lung cancer. Selpercatinib was also found to have a low rate of toxic effects, and treatment-related adverse effects did not require dose modification or treatment interruption. 

Selpercatinib has been found to have significant antitumor activity overall, and the approval of the drug gives a promising treatment option for RET fusion-positive NSCLC patients. 


FDA Approves Lilly’s Retevmo® (selpercatinib), the First and Only RET Inhibitor for Adults with Advanced or Metastatic Solid Tumors with a RET Gene Fusion, Regardless of Type 

Efficacy of Selpercatinib in RET Fusion–Positive Non–Small-Cell Lung Cancer 

RET and Lung Cancer