A Study to Test the Safety of the Investigational Drug Larotrectinib in Adults That May Treat Cancer

The trial will be conducted in 2 parts: an initial dose escalation phase of larotrectinib in
subjects with advanced solid tumors will be followed by an expansion phase in subjects with
solid tumors having a NTRK fusion.

The objectives of the study are to determine the safety, pharmacokinetic profile, recommended
dose and efficacy of orally administered larotrectinib in patients with NTRK fusions.

Inclusion Criteria:

- Adult patients with a locally advanced or metastatic solid tumor that has progressed
or was nonresponsive to available therapies, are unfit for standard chemotherapy or
for which no standard or available curative therapy exists.

- Proof of a malignancy harboring a NTRK fusion

- Eastern Cooperative Oncology Group (ECOG) score of 0, 1 or 2 and a life expectancy of
at least 3 months

- Adequate hematologic, hepatic, and renal function

Exclusion Criteria:

- Patients with unstable primary central-nervous-system tumors or metastasis, exceptions
possible

- Clinically significant active cardiovascular disease or history of myocardial
infarction

- Active uncontrolled systemic bacterial, viral, or fungal infection

- Current treatment with a strong CYP3A4 inhibitor or inducer

- Pregnancy or lactation