Oral Immunomodulatory Tyrosine Kinase Inhibitor in Patients With Locally Advanced or Metastatic Solid Tumors

Inclusion Criteria: 1. Patients with histologically or cytologically confirmed diagnosis of locally advanced or metastatic solid tumor disease for which standard therapy is not effective, available, acceptable, or is intolerable. 2. Dose level 2 (20 mg) and higher: willing to provide baseline and on treatment tumor biopsies (3 weeks after RXDX-106 treatment initiation), provided the procedure is clinically feasible and not deemed unsafe by the investigator. 3. Prior anticancer therapy is allowed, including prior checkpoint inhibitor treatment. 4. Must have measurable disease per RECIST 1.1 as assessed by computed tomography (CT) scan or magnetic resonance imaging (MRI). a. Lesion/s deemed accessible to biopsy for both before and on-treatment biopsies. 5. Males or females aged ≥18 years at screening. 6. Screening laboratory values: 1. Hemoglobin ≥9 g/dL 2. Absolute neutrophil count ≥1500 cells/mm3 3. Platelet count ≥100,000 cells/mm3 4. Total bilirubin ≤1.5 × upper limit of normal (ULN) 5. Aspartate aminotransferase and alanine aminotransferase ≤2.5 × ULN 6. Serum creatinine ≤1.5 mg/dL or estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 7. International Normalized Ratio (INR) or prothrombin time (PT) ≤1.5 × ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants) 8. Activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants) 9. TSH within normal limits at baseline, (if not WLN, then total T3 or free T3 and free T4 should be within normal limits) or stable with treatment. 7. Patients with treated stable CNS metastases that are asymptomatic (including leptomeningeal carcinomatosis) are allowed, if there is no evidence of progression for at least 4 weeks after CNS-directed treatment as ascertained by clinical examination and brain imaging. Patients requiring steroids must be at a stable or decreasing dose (≤10 mg/day dexamethasone or equivalent) for at least 2 weeks prior to the start of treatment. The use of seizure prophylaxis is allowed. 8. Resolution of any clinically significant toxic effects of prior therapy to grade 0 or 1 according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.03 (exception of alopecia and grade 2 peripheral neuropathy). 9. Eastern Cooperative Oncology Group (ECOG) performance status of \<2. 10. Other inclusion criteria apply. Exclusion Criteria: 1. Treated with systemic anticancer therapy or an investigational agent within 2 weeks or 5 half-lives, whichever is shorter, prior to start of study drug treatment. Washout will be 2 weeks for antibody therapy and immunotherapy. 2. Major surgery 21 days or less prior to starting study drug or has not recovered from adverse effects from such procedure. 3. Radiotherapy within 2 weeks prior to start of study drug treatment (palliative radiation or stereotactic radiosurgery within 7 days prior to start of study treatment). Patients must have recovered from all radiotherapy-related toxicities. 4. Has received a live-virus vaccination within 30 days prior to start of study drug treatment. a. Seasonal flu and other inactivated vaccines that do not contain live virus are permitted. 5. Severe or unstable medical condition, such as congestive heart failure (New York Heart Association \[NYHA\] Class III or IV), ischemic heart disease, uncontrolled hypertension, uncontrolled diabetes mellitus, psychiatric condition, as well as an uncontrolled cardiac arrhythmia requiring medication (≥grade 2, according to NCI CTCAE v4.03), myocardial infarction within 6 months prior to starting study treatment, or any other significant or unstable concurrent medical illness that in the opinion of the investigator would preclude protocol therapy. 6. History of non-pharmacologically induced prolonged QTc interval \>480 milliseconds. 7. History of other previous or concurrent cancer that would interfere with the determination of safety or efficacy assessment of RXDX-106 with respect to the qualifying solid tumor malignancy. 8. Major active infection requiring parenteral antibiotics. 9. Known HIV infection or active infection with hepatitis B or C. Patients with unknown status at the time of enrollment must be tested during screening. 10. Unable to swallow oral medication. 11. Active gastrointestinal disease (eg, Crohn's disease, ulcerative colitis, or short gut syndrome) or other malabsorption syndromes that would reasonably impact drug absorption. 12. Active autoimmune disease requiring immunosuppressive treatment or history of autoimmune disease requiring immunosuppressive therapy (e.g. requirement for systemic therapy with \>10 mg/day prednisone-equivalent) or any other concurrent use of immunosuppressive therapy. 13. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment. 14. Active retinal pigment epithelium (RPE)/photoreceptor disorders such as; retinitis pigmentosa, cone-rod dystrophies, Bests dystrophy, Stargardt disease (STGD), macular degeneration. 15. Current participation in another clinical study of an investigational agent, vaccine, or device. Concomitant participation in observational studies is acceptable after sponsor approval.