A Study to Test the Effect of the Drug Larotrectinib in Adults and Children With NTRK-fusion Positive Solid Tumors

The primary objective of this study is to investigate the efficacy of larotrectinib for the
treatment of advanced solid tumors harboring a fusion of neurotrophic tyrosine receptor
kinase (NTRK) of types 1-3 in children and adults.

Secondary objectives comprise the efficacy and safety of larotrectinib in different
NTRK-tumor types.

Inclusion Criteria:

- Locally-advanced or metastatic malignancy with an NTRK1, NTRK2, or NTRK3 gene fusion
identified through molecular assays

- Subjects must have received prior standard therapy appropriate for their tumor type
and stage of disease, or in the opinion of the investigator, would be unlikely to
tolerate or derive clinically meaningful benefit from appropriate standard of care
therapy

- Subjects must have at least one measurable lesion as defined by RECIST v1.1

Exclusion Criteria:

- Prior progression while receiving approved or investigational tyrosine kinase
inhibitors targeting TRK. Subjects who received less than 28 days of treatment and
discontinued because of intolerance or toxicity are eligible.

- Symptomatic or unstable brain metastases. (Note: Subjects with asymptomatic brain
metastases are eligible to participate in the study.) Subjects with primary CNS tumors
are eligible.

- Active uncontrolled systemic bacterial, viral, or fungal infection, unstable
cardiovascular disease, or other systemic disease that would limit compliance with
study procedures.

- Pregnancy or lactation.