A Study of Ivonescimab in People With Leiomyosarcoma

Inclusion Criteria: * Male or female age ≥ 18 years at the time of informed consent * Subjects must have a histologically confirmed unresectable/metastatic LMS * Be willing and able to provide written informed consent/assent for the trial * Be willing to comply with treatment protocol * Adequate performance status: ECOG 0 - 2 * Subjects must have had at least 1 but not more than 3 prior lines of systemic therapy for their LMS. Patients who decline the standard of care first-line systemic therapy will be eligible for this trial. Prior adjuvant therapy will not count provided it was completed more than 6 months previously. * Patients who were treated with radiotherapy must have completed radiation therapy at least 2 weeks before the study drug administration. * Patients who were treated with chemotherapy or any investigational therapies or other anti-cancer agent, if eligible, must have been completed at least 3 weeks or at least 5 half-lives (whichever is longer, but no less than 3 weeks) before the study drug administration. All AEs must be ≤ NCI CTCAE v5 Grade 1, except alopecia and stable neuropathy, which must have resolved to Grade ≤ 2 or baseline. Patients who were treated with estrogen modulating therapies (aromatase inhibitors, tamoxifen, GnRH agonists etc.) must have been treated at least 2 weeks prior to study drug administration. * Participants must have sufficient archival tumor tissue available (most recently procured sample where tissue is available) for research purposes. If archival tumor tissue is insufficient, a pre-treatment research biopsy will be optional but strongly encouraged, if safe and feasible, in the opinion of the Investigator. If biopsy is not feasible and no sufficient archival tissue is available, discussion is required with the Principal Investigator. * Presence of measurable disease per RECIST v1.1. Target lesions must not be chosen from a previously irradiated field unless there has been radiographically and/or pathologically documented tumor progression in that lesion prior to enrollment. * Adequate Organ Function: a. Hematology (no blood transfusions or growth factor therapy used within 7 days of the screening CBC): i. Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L ii. Platelet count ≥ 100 × 10\^9/L iii. Hemoglobin ≥ 9.0 g/dL b. Kidneys: i. Creatinine clearance\* (CrCL) ≥ 50 mL/min using the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) value ≥30 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (adjustment by BSA is not required for eGFR) CrCL or eGFR can be determined using the calculator from the National Kidney Foundation website (www.kidney.org). ii. Urine protein \< 2+ or 24-hour urine protein quantification \< 1.0 g c. Liver: i. Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); For patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤3 × ULN ii. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; For patients with liver metastases, AST and ALT ≤ 5 × ULN * Coagulation: prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 × ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy). This applies only to patients who are not on therapeutic anti-coagulation. Patients receiving therapeutic anti-coagulation should be on a stable dose. * Female patients of childbearing age must have negative serum pregnancy test results before randomization or per region-specific guidance documented in the informed consent and a negative urine pregnancy test on the day of first dose prior to dosing. * Female patient of childbearing potential having sex with an unsterilized male partner must agree to use a highly effective method of contraception from the beginning of screening until 90 days after the last dose of the ivonescimab. * Unsterilized male patients having sex with a female partner of childbearing potential, or a pregnant or breastfeeding partner must agree to use barrier contraception (male condom) for the duration of the treatment period until 90 days after the last dose of ivonescimab. Male patients with female partners of childbearing potential must have the female partner agree to use at least 1 form of highly effective contraception for the duration of the treatment period until 90 days after the last dose of ivonescimab. Exclusion Criteria: * Prior therapy with an anti PD1/PDL1 inhibitor and/or VEGF inhibitor (including multi-tyrosine kinase inhibitors with VEGF inhibition such as pazopanib/cabozantinib/sunitinib). * History or evidence of symptomatic autoimmune disease (e.g., pneumonitis, glomerulonephritis, vasculitis, or other), or history of active autoimmune disease that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive drugs or biological agents used for treatment of autoimmune diseases) in past 2 years prior to enrollment. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment for autoimmune disease. * Evidence of clinically significant immunosuppression such as the following: o Primary immunodeficiency state such as Severe Combined Immunodeficiency Disease o Concurrent opportunistic infection o Receiving systemic immunosuppressive therapy (\> 2 weeks) including oral steroid doses \> 10 mg/day of prednisone or equivalent within 7 days prior to enrollment. However, in the setting of non-immune mediated indications for steroid use, chronic/active low dose steroid use may be permitted at the discretion of the principal investigator. The dose of steroid allowed in this setting is also at the discretion of the principal investigator. (Use of inhaled or topical steroids is permitted.) * Major surgical procedures