• Patients must have a histologically confirmed locally advanced or metastatic, radioactive iodine (RAI) refractory, differentiated thyroid cancer (including papillary, follicular, and oncocytic/Hurthle cell, and poorly differentiated thyroid cancer \[PDTC\]), with progression within 12 months (per Response Evaluation Criteria in Solid Tumors \[RECIST\] version \[v\] 1.1 response criteria) prior to study registration, and no prior therapy in the RAI-refractory setting and for which standard curative or palliative measures do not exist or are no longer effective.

‣ NOTE: RAI refractoriness is defined as absence of uptake of RAI on either a low-dose diagnostic test or a post-treatment RAI scan in measurable lesions or radiographic progression of disease within 12 months of the last course of RAI treatment despite the recorded uptake of RAI with that previous therapy or having a cumulative lifetime administered dose of ≥ 600mCi.

⁃ Poorly differentiated thyroid cancer (PDTC) is typically classified as a type of differentiated thyroid cancer (as opposed to undifferentiated thyroid cancer or anaplastic thyroid cancer)

• Patients must have measurable disease according to RECIST v 1.1

• Patients must be age ≥ 18 years

• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance score of ≤ 2

• Leukocytes (WBC) ≥ 3,000/mcL

• Absolute neutrophil count (ANC) ≥ 1,500/mcL

‣ Prophylactic use of granulocyte colony-stimulating factor (G-CSF) will not be allowed within 2 weeks of relevant screening laboratory testing. However, G-CSF may be employed in accordance with current American Society of Clinical Oncology (ASCO) guidelines for treatment-emergent neutropenia observed at any time during the study

• Hemoglobin (Hgb) ≥ 9 g/dL

‣ Prophylactic use of blood transfusions for anemia and thrombocytopenia is not allowed within 2 weeks prior to relevant screening laboratory testing, but such treatment is allowed for treatment-emergent anemia or thrombocytopenia, as indicated by the current ASCO and American Association of Blood Banks guidelines

• Platelets (PLT) ≥ 100,000/mcL

‣ Prophylactic use of blood transfusions for anemia and thrombocytopenia is not allowed within 2 weeks prior to relevant screening laboratory testing, but such treatment is allowed for treatment-emergent anemia or thrombocytopenia, as indicated by the current ASCO and American Association of Blood Banks guidelines

• Total bilirubin ≤ 1.5 x Institutional upper limit of normal (ULN) ; for subjects with Gilbert's disease ≤ 3 x ULN

• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) ≤ 3 x Institutional ULN

• Alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 x Institutional ULN

• ALP (alkaline phosphatase) ≤ 3 x Institutional ULN; For subjects with documented bone metastasis, ≤ 5 x ULN

• Creatinine Clearance (CrCl) ≥ 40 mL/min (≥ 0.67 mL/sec) using the Cockcroft-Gault equation

• International Normalized Ratio (INR) ≤ 1.5 x Institutional ULN (in patients not currently on therapeutic anticoagulation)

• Activated partial thromboplastin time (aPTT) ≤ 1.2 × Institutional ULN (in patients not currently on therapeutic anticoagulation)

• Urine protein-to creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.1 mg/mmol)

• For patients with a known history of human immunodeficiency virus (HIV), infected patients on effective anti-retroviral therapy must have a viral load undetectable for 6 months prior to registration. Please note this lab is not a requirement for eligibility, however, if it has been completed previously as part of the patient's health care, it should be documented for eligibility.

‣ NOTE. To be eligible, patients must not have known uncontrolled infection with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness

⁃ NOTE: patients must meet all of the following criteria:

• On stable anti-retroviral therapy

∙ CD4+ T cell count ≥ 200/µL; and

∙ An undetectable viral load.

⁃ NOTE: HIV testing will be performed at screening if it is required by local regulation or per standard of care (SOC).

⁃ NOTE: To be eligible, patients taking CYP inhibitors (e.g., zidovudine, ritonavir, cobicistat, didanosine) or CYP3 inducers (efavirenz) must change to a different regimen not including these drugs 7 days prior to initiation of study treatment. Anti-retroviral therapies (ART) must have been received for at least 4 weeks prior to the first dose.

⁃ NOTE: CD4+ T cell counts, and viral load are monitored per standard of care by the local health care provider

• Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression and patients are stable for at least 4 weeks before the first dose of study treatment.

‣ NOTE: Patients with active brain metastases are not allowed.

⁃ NOTE: Therapeutic doses of Low Molecular Weight Heparin (LMWH) are not permitted in patients with known brain metastases

• Patients of child-bearing potential must have a negative pregnancy test prior to registration on study.

‣ NOTE: Patients of child-bearing potential are considered to be of child-bearing potential unless one of the following criteria are met: documented permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) or documented postmenopausal status (defined as 12 consecutive months of amenorrhea in a patient of child-bearing potential \> 45 years-of-age in the absence of other biological or physiological causes). In addition, a patient of child-bearing potential \< 55 years-of-age must have a serum follicle stimulating hormone (FSH) level \> 40 mIU/mL to confirm menopause)

• The effects of XL092 on the developing human fetus are unknown. For this reason and because tyrosine kinase inhibitors (TKIs) as well as other therapeutic agents used in this trial are known to be teratogenic, sexually active fertile patients and their partners must agree to use highly effective methods of contraception during the course of the study and for the following durations after the last dose of study treatment (whichever is later): Through 186 days after the last dose of XL092 for patients of child-bearing potential or through 96 days after the last dose of XL092 for patients of sperm producing capacity. Because the effect of XL092 on the pharmacokinetics (PK) of contraceptive steroids has not been investigated, hormonal contraceptives may not achieve the level considered highly effective. For this reason, an additional contraceptive method, such as a barrier method (e.g., condom), may be required. In addition, patients of sperm producing capacity must agree not to donate sperm and patients of child-bearing potential must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods. Should a patient of child-bearing potential become pregnant or suspect they are pregnant while they or their partner are participating in this study, they should inform their treating physician immediately

• Recovery to baseline or ≤ grade 1 per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5 from adverse events (AE\[s\]) related to any prior treatments unless AE(s) are deemed clinically nonsignificant by the Treating Investigator and/or stable on supportive therapy.

‣ NOTE: Patients must have recovered from adverse events due to prior anti-cancer therapy (i.e., have residual toxicities \> grade 1) except for alopecia, neuropathy, and other non-significant adverse events per NCI CTCAE v 5.0

• Patients must have the ability to understand and the willingness to sign a written informed consent document and comply with the protocol requirements

• Patients must have the ability to swallow, retain and absorb oral medications

‣ NOTE: Patients must have the ability to swallow tablets or ingest a suspension either orally or by a nasogastric (NG) or gastrostomy (PEG) tube