• Histologically or cytologically confirmed soft tissue sarcoma that is metastatic or unresectable.

• Must have received at least one but no more than 3 lines of therapy in the metastatic setting, with progression on last line of therapy. Neoadjuvant or adjuvant therapy completed more than one year prior does not count towards as a line of therapy in the metastatic. Individuals with alveolar soft part sarcoma may enroll without being refractory to at least one line of therapy.

• Measurable disease per RECIST 1.1.

• At least 18 years of age.

• ECOG performance status ≤ 1.

• 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 prior to screening laboratory collection

⁃ Platelets ≥ 100 K/cumm without transfusion within 2 weeks prior to screening laboratory collection

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

⁃ INR ≤ 1.5 and aPTT ≤ 1.2 x IULN. For subjects on Factor Xa inhibitors, criteria does not apply.

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

⁃ AST(SGOT), ALT(SGPT), and alkaline phosphatase (ALP) ≤ 3.0 x IULN. For subjects with documented bone metastasis, ALP ≤ 5.0 x IULN.

⁃ Serum albumin ≥ 2.8 g/dL.

⁃ Calculated creatinine clearance ≥ 40 mL/min by Cockcroft-Gault.

⁃ UPCR ≤ 1 mg/mg (≤ 113.2 mg/mmol) creatinine.

• Recovery to baseline or ≤ grade 1 from AEs, including immune-related AEs related to any prior treatments, unless AEs are clinically nonsignificant and/or stable on supportive therapy (e.g., 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. In addition, men must agree not to donate sperm and women must agree not to donate eggs (ova, oocyte) for the purpose of reproduction during these same periods:

‣ 186 days after last dose of zanzalintinib (for women) or 96 days after last dose of zanzalintinib (for men).

⁃ 5 months after the last dose of nivolumab or 3 months after the last dose of ipilimumab.

• 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.