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 an experimental 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 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.

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.

Lead Organization
Bayer Corporation

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