Investigational Drug LOXO-292 Is Safe and Effective in Pediatric RET-Mutated Cancers

LOXO-292 is an oral and selective investigational novel drug for the treatment of cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. Genomic alterations of RET kinase have been identified as oncogenic drivers in pediatric and adult cancers.

In an ongoing phase I/II study of adult and adolescent patients with advanced RET-altered cancers, LOXO-292 demonstrated marked antitumor activity and was well tolerated. A real-world study presented at the 2019 ASCO Annual Meeting included pediatric patients with RET-altered cancers who were unable to access LOXO-292 through a phase I/II clinical trial but were enrolled using U.S. Food and Drug Administration-allowed, Investigational Review Board-approved single patient protocols.

Patients received LOXO-292 (capsule/liquid formulation) orally and continuously at a starting dose of 90 mg/m2 twice daily.  As of January 31, 2019, four female patients aged 13 months to 8 years were enrolled from the Republic of Korea and the United States. Patients had papillary thyroid cancer (n=1), infantile myofibroma/hemangiopericytoma (n=1), congenital mesoblastic nephroma/infantile fibrosarcoma (n=1), and lipofibromatosis (n=1). All tumors harbored RET gene fusions that were confirmed with next-generation sequencing. Previous courses of treatment included surgery/iodine 131 (n=1), vandetanib (n=1), and surgery/chemotherapy (n=1). One patient was treatment-naïve.

All patients remained on treatment, and treatment duration ranged from three to 120 days. No patients required dose modifications or discontinued treatment due to adverse events (AEs). There were no treatment-related grade ≥3 AEs. Two patients who were evaluable for response had partial responses, both of which were ongoing. One was confirmed, while the other was pending confirmation.

“These preliminary data from a real-world setting suggest that LOXO-292 is effective and safe in pediatric patients whose tumors harbor RET gene fusions,” the researchers concluded.


Gerdemann U, Lee YA, Henry D, et al. First experience of LOXO-292 in the management of pediatric patients with RET-altered cancers. Abstract #10045. Presented at the 2019 ASCO Annual Meeting, Chicago, IL, June 1, 2019.