LOXO-RET-18036: A Phase 1/2 Study of the Oral RET Inhibitor LOXO-292 in Pediatric Patients with Advanced Solid or Primary Central Nervous System Tumors

This is a multicenter, open-label, Phase 1/2 study in pediatric patients with an activating ReT alteration and an advanced solid or primary central nervous system (CnS) tumor. LoXo-292 will be administered orally twice daily (BiD), with the dose adjusted by body surface area (BSa). This trial will use a Rolling 6 Dose escalation scheme. a minimum of 3 patients will enroll in Dose Levels 1 and 2, also referred to as Dose Cohorts 1 and 2, respectively. each patient in a given cohort must have completed safety assessments through Cycle 1, Day 28 (C1D28), and received a minimum of 75% of the planned total dose in Cycle 1 (unless due to toxicity) to be eligible for the assessment of dose limiting toxicity (DLT). (if the first 2 patients within a cohort experience a DLT prior to enrollment of the third patient, the third patient will not be enrolled.). if no DLT then accrual in the next highest cohort will begin immediately. if the first 3 patients have not cleared the DLT window, additional patients may be enrolled on the current dose level up to a maximum of 6. a minimum of 3 patients in a given cohort must have completed 28 days of safety assessment in Cycle 1 without DLT and a maximum of 1 DLT in 6 patients who have completed the DLT window before the next cohort initiates accrual. escalation will proceed through the 3 dose levels until the MTD or recommended dose for expansion is reached. Based on the interim evaluation of the safety and tolerability data of the previous cohort, it may be decided to enroll additional patients in a previously studied cohort or at an intermediate dose level. LoXo-292 is administered in oral capsule or liquid suspension. each cycle consists of 28 days. General Treatment Procedures may be found in section 3.1.1.1 of the protocol