The experimental treatment LOXO-101 led to remarkable improvement for a 20-month-old girl whose rare pediatric cancer did not respond to surgery or chemotherapy, according to a report published in Pediatric Blood & Cancer.1

“Most infants and children with infantile fibrosarcoma (IFS) can be cured through surgery and chemotherapy. When our patient’s disease progressed in spite of these treatments, we had to investigate new options that could target the disease,” said Ramamoorthy Nagasubramanian, MD, division chief of pediatric hematology-oncology at Nemours Children’s Hospital in Orlando, Florida, and lead author of the report.

“The dramatic reduction in tumor size shows early but promising evidence of the potential for LOXO-101 to provide significant benefit for pediatric patients with NTRK gene fusions.”

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Nemours’ oncology team operated on the girl at 6 months to remove a large tumor located in the neck and face. Unfortunately, the tumor did not respond to standard chemotherapy and relapsed after extensive surgery.

Genetic testing confirmed an ETV6-NTRK3 gene fusion, which is frequently found in IFS. At the time, LOXO-101 was in a phase 1 multicenter basket trial in adults. Working with Nemours, Loxo Oncology, Inc., a biopharmaceutical company developing highly selective medicines for patients with genetically defined cancers, was able to expand the trial to children and enroll her.

The researchers developed a special liquid formulation of LOXO-101 and took a pharmacokinetic approach that weighed all the variables, to determine the proper size dosage for each case. Response to the drug was assessed by MRI imaging every 4 to 8 weeks.

“Although some genetic drivers of cancer are found in both pediatric and adult patients, there are few targeted therapies available to children with cancer,” said Josh Bilenker, MD, chief executive officer of Loxo Oncology. “We’ve known that NTRK fusions play an important role in many pediatric cancers, and this case study is a first step in demonstrating that a selective TRK inhibitor can provide benefit to these children. We are dedicated to the rapid development of LOXO-101 in pediatric cancer patients.”

When the research was published, the patient was in her fifth cycle of LOXO-101. She is achieving normal developmental milestones. In addition, she has not experienced any adverse events related to LOXO-101.

The authors stated that this case report indicates the importance of targeted therapies for pediatric patients “when compelling oncogenic drivers can be identified and potent investigational inhibitors are available.”

“The development of these inhibitors for pediatric patients has likely lagged behind adult development because of the limited availability of comprehensive genomic profiling of rare pediatric tumors, and the generally favorable outcomes of using conventional treatments,” said Nagasubramanian. “However, this case underscores the promise and life-saving potential of targeted therapies for children.”


1. Nagasubramanian R, Wei J, Gordon P, et al. Infantile fibrosarcoma with NTRK3–ETV6 fusion successfully treated with the tropomyosin-related kinase inhibitor LOXO-101 [published online ahead of print April 19 2016]. Pediatr Blood Cancer. doi:10.1002/pbc.26026.