Study of Molecular Profile-Related Evidence to Determine Individualized Therapy for Advanced or Poor Prognosis Cancers

Inclusion Criteria Patients must meet all of the inclusion criteria to participate in this study. 1. Patients with incurable malignancies with more than 50% 2-year cancer-associated mortality (as estimated by two physician and where appropriate according to 2014 National Cancer database) Diseases include, but are not limited to: Ampullary carcinoma Intrahepatic cholangiocarcinoma (IHCC) Appendiceal cancer Melanoma Colorectal cancer (CRC) Non-KIT GIST (gastrointestinal stromal tumor) Extrahepatic cholangiocarcinoma (EHCC) Non-small cell lung cancer (NSCLC) Esophageal adenocarcinoma Ovarian cancer Gallbladder cancer (GBCA) Pancreatic ductal adenocarcinoma (PDAC) Gastric adenocarcinoma Sarcoma (high-grade) Head and neck cancer Small bowel adenocarcinoma (including duodenal) Hepatocellular carcinoma (HCC) Triple-negative breast cancer (TNBC) Urothelial cancer 2. Patients with cancer of unknown primary or a rare tumor (for example, fewer than 15 cases per 100,000 per year) with no approved therapies. (Patients in this inclusion criteria must meet all other exclusion and inclusion criteria except inclusion criteria #1) 3. Patients with incurable malignancies, irrespective of 2-year mortality, who, in the opinion of the investigator have no treatment option expected to yield significant clinical benefit." 4. Patients must have at least one of the following for a diagnosis/disease status: 1. Unresectable disease 2. Metastatic disease 3. Medically unfit for surgical resection but with an expected survival of \> 3 months, ECOG \< 2 and NYHA status ≤ II (refer to status definitions in tables below) 4. Disease where no conventional therapy leads to a survival benefit \> 6 months in the respective cohort and line of therapy for which the patient is otherwise eligible 5. Actionable alterations determined by FoundationOneTM 5. Treatment naïve for his or her newly diagnosed malignancy for enrollment to Groups 1 or 2. 6. Status post 1 or more unmatched systemic therapy regimens for enrollment to Group 3. 7. Ability to understand and the willingness to sign a written informed consent. 8. Patients must have measurable disease for malignancies: defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm with conventional techniques or as ≥10 mm with spiral CT scan, PET-CT, MRI, or calipers by clinical exam. 9. Age ≥ 18 years. 10. ECOG Performance Status 0-1. Grade Description 0 Fully active, able to carry on all pre-disease performance without restriction 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework or office work 2 Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about \>50% of waking hours 3 Capable of only limited self-care, confined to a bed or chair \>50% of waking hours 4 Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair 5 Dead 11. New York Heart Association (NYHA) Functional Classification I-II. NYHA Class Symptoms I Cardiac disease, but no symptoms and no limitation in ordinary physical activity, e.g. shortness of breath when walking, climbing stairs etc. II Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. III Marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m). Comfortable only at rest. IV Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. 12. Adequate organ and marrow function as defined below: * Absolute neutrophil count ≥ 1.5 x 109/L * Platelet count ≥ 100 x 109/L * Total bilirubin ≤ 2.0 x institution's ULN * Patients without underlying liver disease o ALT and AST ≤ 2.5 X institutional upper limit of normal * Serum creatinine ≤ 2.0 x institution's ULN or 24-hour creatinine clearance ≥ 50 ml/min 13. At the time of treatment, patients should be off other anti-tumor agents for at least 5 half-lives of the agent or 3 weeks from the last day of treatment, whichever is shorter to enroll in Group 3. Patients must not have been treated with anti-tumor agents to enroll in Group 1 or Group 2. Patients must be off prior antibody therapy for at least 3 half-lives before starting treatment. Patients may enroll on study even while receiving treatment. 14. Able to swallow and retain oral medication if needed. 15. Patients must have evaluable tissue/blood for testing as specified by the concurrent FoundationOneTM criteria. This will be obtained during the standard of care tumor diagnosis and tumor staging evaluation. 16. Female patients of childbearing potential must have a negative serum pregnancy test and agree to use at least one form of pregnancy prevention during the study and for at least one month after treatment discontinuation. For the purposes of this study, child- bearing potential is defined as: all female patients that were not in post- menopause for at least one year or are surgically sterile (site-specific criteria applying to Avera only) 17. Male patients must use a form of barrier pregnancy prevention approved by the investigator / treating physician during the study and for at least one month after treatment discontinuation (site-specific criteria applying to Avera only). Exclusion Criteria Subjects meeting any of the exclusion criteria at baseline will be excluded from study participation. 1. Two oncologists disagree on prognosis or resectability. 2. Severe or uncontrolled medical disorder that would, in the investigator's opinion, confound study analyses of treatment response (i.e., uncontrolled diabetes, chronic renal disease, chronic pulmonary disease or active, uncontrolled infection, psychiatric illness/social situations that would limit compliance with study requirements). 3. Are pregnant or breast-feeding patients or any patient with childbearing potential not using adequate pregnancy prevention (site-specific criteria applying to Avera only).