Inclusion Criteria:

• Histologically- or cytologically-confirmed diagnosis of locally advanced or metastatic solid tumor that harbors an NTRK1/2/3, ROS1, or ALK gene rearrangement

  - Note: Patients diagnosed with anaplastic large cell lymphoma (ALCL) harboring a gene rearrangement of interest may be eligible provided they meet all other inclusion/exclusion criteria

• For patients enrolled via local molecular testing, an archival or fresh tumor tissue (unless medically contraindicated) is required to be submitted for independent central molecular testing at Ignyta's CLIA laboratory post-enrollment
• Measurable or evaluable disease
• Patients with CNS involvement, including leptomeningeal carcinomatosis, which is either asymptomatic or previously-treated and controlled, are allowed
• Prior anticancer therapy is allowed (excluding approved or investigational Trk, ROS1, or ALK inhibitors in patients who have tumors that harbor those respective gene rearrangements)

  - Note: prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are prohibited.

• At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed after prior chemotherapy or small molecule targeted therapy
• At least 4 weeks must have elapsed since completion of antibody-directed therapy
• Prior radiotherapy is allowed if more than 14 days have elapsed since the end of treatment
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 and minimum life expectancy of 4 weeks
• Adequate organ function as defined per protocol
• Ability to swallow entrectinib intact
• Other protocol specified criteria

Exclusion Criteria:

• Current participation in another therapeutic clinical trial
• Prior treatment with approved or investigational Trk, ROS1, or ALK inhibitors in patients who have tumors that harbor those respective gene rearrangements

  - Note: prior treatment with crizotinib is permitted only in ALK- or ROS1-rearranged NSCLC patients presenting with CNS-only progression. Other ALK inhibitors are prohibited.

• History of other previous cancer that would interfere with the determination of safety or efficacy
• Incomplete recovery from any surgery
• History of non-pharmacologically induced prolonged QTc interval
• History of additional risk factors for torsade de pointes
• Peripheral neuropathy Grade ≥ 2
• Known active infections
• Active gastrointestinal disease or other malabsorption syndromes
• Known interstitial lung disease, interstitial fibrosis, or history of tyrosine kinase inhibitor-induced pneumonitis
• Other protocol specified criteria