Dr. Drilon Discusses Efficacy Results With LOXO-292 in RET-Altered Solid Tumors

Alexander Drilon, MD, medical oncologist, clinical director, Early Drug Development Service, Memorial Sloan Kettering Cancer Center, discusses findings from the phase I LIBRETTO-001 study exploring the highly selective RET inhibitor LOXO-292 in patients with RET-altered solid tumors in an interview with OncLive during the 2018 ASCO Annual Meeting.

In the ongoing study, LOXO-292 demonstrated clinical activity across RET-altered solid tumors, including in patients with brain metastases and the RET V804M gatekeeper mutation, which usually confers resistance to multikinase inhibitors. There were findings reported in both biologic subsets, which were RET fusion-positive cancers and RET-mutant cancers. The RET fusion-positive cancers cohort was comprised of lung cancer, thyroid cancer, and pancreatic carcinomas, and was associated with a response rate of 74%, explains Drilon. In RET-mutant cancers, which consisted of medullary thyroid cancers, the confirmed response rate was 33%. With prior studies in these patient populations and less-selective therapies, the response rates were approximately 30% with more toxicity in RET fusion-positive cancers.

Regarding safety, LOXO-292 had a low frequency in treatment-emergent adverse events (TRAEs), which were mainly grade 1/2, many of which were not related to LOXO-292, says Drilon. The TRAEs were mainly mild cases of fatigue and gastrointestinal effects. There was one dose-limiting toxicity in a patient who developed tumor lysis syndrome and one grade AE of an increase in liver function tests.

<<< 2018 ASCO Annual Meeting