LOXO - 101

Primary objectives

Phase I
-To characterize the PK properties of larotrectinib in pediatric patients with advanced solid or primary CNS tumors
-To identify the MTD and/or the appropriate dose of larotrectinib for further clinical investigation in this patient population
-To describe the antitumor activity of larotrectinib
-To describe pain and health related quality of life (HRQoL)

Phase II
-To determine the ORR based on the treating Investigator’s response assessment using RECIST 1.1 or RANO criteria, as appropriate to tumor type

Secondary objectives

Phase I:
-To evaluate potential biomarkers of response and resistance to larotrectinib

Phase II
-To determine the ORR based on the treating Investigator’s response assessment using RECIST 1.1 or RANO criteria, as appropriate to tumor type
-To evaluate the duration of response (DOR) in patients with best overall response of
-CR or PR as determined by 1) an independent radiology review committee and 2) the treating Investigator
-To estimate the proportion of patients that has any tumor regression as a best response
-To evaluate the duration of progression-free survival (PFS) following initiation of larotrectinib
-To evaluate the duration of OS following initiation of larotrectinib
-To asess the safety profile and tolerability of larotrectinib

• Children from 0 to 21 with a locally advanced or metastatic infantile fibrosarcoma with a positive ETS variant gene 6 (ETV6) break-apart fluorescence in situ hybridization (FISH) or other appropriate molecular analysis.
• 0 through 21 years with a locally advanced or metastatic solid tumor or primary CNS tumor that has relapsed, progressed or was nonresponsive to available therapies and for which no standard or available systemic curative therapy exists with a documented NTRK gene fusion
• at least one measurable lesion as defined by RECIST or RANO
• Karnofsky or Lansky > 50

• Major surgery within 14 days (2 weeks) prior to C1D1…
• Clinically significant active cardiovascular disease or history of myocardial infarction within 6 months prior to C1D1; ongoing cardiomyopathy; or current prolonged QT interval