• Diagnosis of recurrent, FIGO grade 3 endometrioid, serous, or mixed high grade uterine or endometrial cancer or uterine carcinosarcoma. Patients must have experienced either prior progression on a platinum-based therapy or intolerance to platinum. Patients with dMMR or MSI-H tumors or targetable HER2 alterations are required to have received prior therapy with appropriate targeted agents.

• 1-2 prior lines of anti-cancer therapy are allowed.

• Subjects who have received prior treatment with trastuzumab, pembrolizumab, or dostarlimab can enroll in the study. Use of these agents together or as maintenance therapy is considered 1 regimen.

• 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)

• Patients must have disease that cannot be managed by local therapy targeted at the tumor site (i.e. surgery, radiation therapy).

• Measurable disease by RECIST 1.1.

• At least 18 years of age.

• ECOG performance status ≤ 2.

• Adequate bone marrow and organ function within 14 days prior to first dose of study treatment, as defined below:

‣ Absolute neutrophil count ≥ 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 of screening laboratory sample collection.

⁃ Hemoglobin ≥ 9.0 g/dL without transfusion within 2 weeks prior to screening laboratory sample collection.

⁃ Total bilirubin ≤ 1.5 x IULN (for subjects with Gilbert's disease ≤ 3 x ULN).

⁃ Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x ULN. For subjects with documented bone metastasis ALP ≤ 5 x ULN. Serum creatinine \< 1.5 x ULN OR calculated or measured creatinine clearance ≥ 40 mL/min (using Cockcroft-Gault equation)

⁃ INR ≤ 1.5 x IULN

⁃ aPTT ≤ 1.2 x IULN

⁃ Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine

• Female subjects of child-bearing 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. Should a patient become pregnant or suspect pregnancy while participating in this study, the treating physician must be informed immediately.

• The effects of zanzalintinib on the developing human fetus are unknown. For this reason and because chemotherapeutic agents are known to be teratogenic, patients of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and through 186 days after last dose of zanzalintinib or paclitaxel for women of child-bearing potential (WOCBP). An additional contraceptive method, such as a barrier method (eg, condom), is required. In addition, women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods.

• 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.