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

This research study is done to test how well different types of cancer respond to the drug called larotrectinib. The cancer must have a change in a particular gene (NTRK1, NTRK2 or NTRK3). Larotrectinib is a drug that blocks the actions of these NTRK genes in cancer cells and can therefore be used to treat cancer.

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

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.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Bayer Corporation

• Primary ID 20289
• Secondary IDs NCI-2015-01947, LOXO-TRK-15002, 2015-003582-28
• Clinicaltrials.gov ID NCT02576431