LOXORET: Phase I/II Study of LOXO-292 (Selpercatinib) in Patients with Advanced RET-Altered Solid Tumors or Brain Tumors

Brief Summary

LOXORET is an open-label, multi-center Phase I/II study of oral selpercatinib in pediatric patients with an activating RET gene alteration and an advanced solid or primary CNS tumor.

RET is a receptor tyrosine kinase (RTK). LOXO-292 is a small molecule designed to block the adenosine triphosphate (ATP) binding site of the RET RTK. Preclinical data suggest it inhibits tumor growth in RET-dependent tumor models, with minimal inhibition of other kinase and non-kinase off targets.

This study includes two parts: Phase I (dose escalation) and Phase II (dose expansion). In Phase I, patients will be enrolled using a rolling 6 dose escalation scheme. Once the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) is identified, patients will be enrolled to one of four dose expansion cohorts, depending on tumor histology and tumor genotype. .

Primary Objective

• To determine the safety of oral selpercatinib in pediatric patients with advanced solid tumors and primary CNS tumors

Eligibility Criteria

• 6 months to 21 years old
• Advanced or metastatic solid or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and/or for which no standard or available curative therapy exists
• Evidence of an activating RET gene alteration in the tumor and/or blood
• Patients with primary CNS tumors or cerebral metastases must be neurologically stable for 7 days prior and must not have required increasing doses of steroids within the last 7 days.

Exclusion Criteria include:

• Major surgery within 14 days prior to planned start of selpercatinib
•  Clinically significant, uncontrolled cardiac, cardiovascular disease or history of myocardial infarction within 6 months prior to planned start of selpercatinib
•  Pregnant or breastfeeding
• Current treatment with proton pump inhibitors
• Active infection
• Active malabsorption syndrome

Study Sites

St. Jude Children’s Research Hospital, Memphis, Tennessee
Collaborating sites in the U.S.

About this study

This study will test the safety of an experimental drug treatment in children and adolescents with advanced solid tumors or brain and spinal cord tumors.

Many children with these tumors are helped by standard cancer treatments, such as chemotherapy, radiation and surgery. However, some children do not respond to treatment or their cancer comes back after therapy. This study is for children with these kinds of advanced tumors.

The drug in this clinical trial is designed to treat solid and brain tumors that have an abnormality in the RET gene. Genes tell the cells of our bodies how to grow, develop and function. 

The name of the experimental drug is selpercatinib. This study is the first time LOXO-292 will be used in children.

Purpose of this clinical trial

The main goal of this study is to test the safety of selpercatinib in children and adolescents with solid tumors or brain and spinal cord tumors. Researchers also want to learn how the drug affects cancer in children and the best, most effective dose.

Eligibility overview

• 6 months to 21 years old
• Solid tumor or brain tumor that has progressed or spread
• Failed standard treatment
• RET gene alteration