The results of a phase 1/2 study testing the safety and appropriate dosage of a drug for treating TRK fusion pediatric cancers have been published in The Lancet. TRK fusions, mutations involving the NTRK1, NTRK2, or NTRK3 genes, are found in a broad range of cancers in pediatric and adult patients. Larotrectinib (LOXO-195), a small molecule TRK kinase inhibitor, had recently been shown to be promising for treating adults with TRK fusion tumors. This study focused on the safety of the same drug in pediatric patients.
The multi-site study across eight locations in the United States included infants and children from 1 month to 21 years of age. The study included 24 patients with an average age of four to five years. Of those patients, 17 had TRK fusion tumors and seven patients did not have the mutation. TRK fusion positive patients had one of three cancer types--infantile fibroscarcoma, other soft tissue sarcoma, or papillary thyroid cancer.
The results overall found that LOXO-195 was well tolerated in patients and had anti-tumor activity in all TRK fusion-positive tumors. Of all patients with TRK fusion-positive tumors, more than 90 percent achieved “sustained tumor regressions,” and none of the patients without TRK fusion tumors experienced any anti-tumor activity. The study findings resulted in a recommended phase 2 dose of 100mg/m2 (maximum 100 mg per dose) for infants, children, and adolescents regardless of their age.
"The TRK gene mutation can be common in pediatric cancers, especially those that are treatment resistant. When we saw this drug was showing promise of anti-tumor activity in adults with TRK fusion tumors, we were hopeful for a similar result for children. Both primary objectives of this study--safety and identifying dosing--were successfully met," said Ramamoorthy Nagasubramanian, MD, an author of the study and division chief of pediatric hematology-oncology at Nemours Children's Hospital.