Zanzalintinib Maintenance in Patients With High Grade Neuroendocrine Neoplasms (HG-NENs)

Inclusion Criteria: * Histologically or cytologically confirmed high-grade poorly differentiated or well differentiated neuroendocrine tumor (with a Ki-67 of ≥20%), excluding small cell lung cancer (SCLC) and Merkel cell cancer. High-grade includes any neuroendocrine neoplasm with a Ki-67 of \>20% or with mitotic count of more than 20 mitoses per high power field or any poorly differentiated neoplasm or any neoplasm lacking these that is deemed high grade by pathology consensus, based on other markers (necrosis or IHC demonstrating p53 or RB mutation). This includes: * High-grade well-differentiated neuroendocrine neoplasms * Transformed NENs from a lower to a higher grade (patient may have some low grade and some high grade NENs) * High-grade neoplasms with significant expression of neuroendocrine markers such as synaptophysin, chromogranin or INSM-1 or unknown origin neoplasms with gene expression signatures consistent with neuroendocrine lineage (as per validated tissue of origin testing, such as CancerType ID, after pathology consensus). * Mixed neuroendocrine and non-neuroendocrine neoplasms (MiNEN), including MiNEN per WHO and mixed neoplasms not fulfilling criteria of MiNEN. The neuroendocrine component would need to be a high-grade neuroendocrine tumor as documented by pathology review. * Note: For ambiguous cases, will consult with a designated expert pathologist. * Measurable disease per RECIST 1.1. * Current or prior somatostatin analogue therapy is allowed if clinically indicated. * Patients must have received their initial course of chemotherapy and be eligible for a chemotherapy break with the most recent disease imaging assessment showing stable disease (SD) or a partial response (PR) by RECIST 1.1. The imaging showing stable disease or partial response should have occurred either during the chemotherapy or right after discontinuation of the chemotherapy treatment and before any other treatment. Reasons for treatment break can include physician or patient preference, completion of pre-specified treatment cycles, or toxicity. Patients intolerant of chemotherapy may also be eligible for the study, but they must have been treated with at least 2 cycles of chemotherapy and at least one imaging assessment on treatment or right after treatment showing PR or SD per RECIST 1.1. There is no limit for prior lines of non-chemotherapeutic regimens (including targeted agents, immunotherapy or radioligand treatment), but the most recent treatment prior to study initiation must contain chemotherapeutic agents. * At least 18 years of age. * ECOG performance status ≤ 2 (Karnofsky ≥ 80%). * Adequate bone marrow and organ function as defined below: * Absolute neutrophil count (ANC) ≥ 1.5 K/cumm without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection. * Platelets ≥ 100 K/cumm without transfusion within 2 weeks prior to screening laboratory sample collection. * Hemoglobin ≥ 9.0 g/dL without transfusion within 2 weeks prior to screening laboratory sample collection. * International Normalized Ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.2 x IULN. * Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease, total bilirubin ≤ 3 x IULN). * Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), and alkaline phosphatase (ALP) ≤ 3.0 x IULN. For subjects with documented bone metastasis, ALP ≤ 5.0 x IULN. * Creatinine ≤ 1.5 x IULN OR calculated creatinine clearance ≥ 40 mL/min by Cockcroft-Gault equation. * Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤113.2 mg/mmol) creatinine. * Recovery to baseline or ≤ Grade 1 severity (CTCAE v5) from adverse events (AEs), including immune-related adverse events (irAEs), related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy (eg, physiological replacement of corticosteroid). Low-grade or controlled toxicities such as alopecia, ≤ Grade 2 hypomagnesemia, ≤ Grade 2 neuropathy are permitted. * Sexually active fertile subjects and their partners must agree to use highly effective method of contraception during the course of the study and for the following durations after the last dose of treatment (whichever is later). An additional contraceptive method, such as a barrier method (eg, condom), is required with use of oral contraceptives. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction through 186 days after the last dose of zanzalintinib for women of childbearing potential (WOCBP) or through 96 days after the last dose of zanzalintinib for men. * Female subjects of childbearing potential must not be pregnant at screening. Female subjects are considered to be of childbearing potential unless one of the following criteria is met: * permanent sterilization (hysterectomy, bilateral salpingectomy, or bilateral oophorectomy) OR * documented postmenopausal status (defined as 12 months of amenorrhea in a woman \> 45 years-of-age in the absence of other biological or physiological causes. In addition, females \< 55 years-of-age must have a serum follicle stimulating hormone \[FSH\] level \> 40 mIU/mL to confirm menopause). * Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff. * Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants. Exclusion Criteria: * Prior treatment with zanzalintinib (XL092) or cabozantinib (XL184). * Another malignancy that requires active therapy and in the opinion of the Investigator would interfere with monitoring of radiologic assessments of response to Investigational Product, within 2 years before C1D1, except for superficial skin cancers, or localize