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

Open to people ages 18 years and up

• Locally advanced or metastatic non-secretory breast cancer, lung cancer, melanoma, and colorectal cancer with unknown human neurotrophic tyrosine receptor kinase 1 (NTRK1), NTRK2, or NTRK3 fusion status.
• 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 Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

• Prior progression while receiving approved or investigational tyrosine kinase inhibitors targeting tropomyosin receptor kinase (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 central nervous system (CNS) tumors are eligible.
• Pregnancy or lactation.
• Active uncontrolled systemic bacterial, viral, or fungal infection Common Terminology Criteria for Adverse Events(CTCAE) grade ≥ 2; unstable cardiovascular disease, or other systemic disease that would limit compliance with study procedures.

Unstable cardiovascular disease is defined as:

• In adults, persistently uncontrolled hypertension defined as systolic blood pressure (BP) > 150 mmHg and/or diastolic BP > 100 mmHg despite antihypertensive therapy.
• Myocardial infarction within 3 months of screening.
• Stroke within 3 months of screening.