Pilot Study of Ivonescimab in Advanced/Metastatic Cutaneous Angiosarcoma

Inclusion Criteria: * Patients must have histologically confirmed cutaneous angiosarcoma that is advanced, metastatic or unresectable. * Patients must have received prior paclitaxel or docetaxel containing therapy. * Patients must have measurable disease within 28 days of starting treatment, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, PET or calipers by clinical exam/medical photography. * Age ≥18 years. Because no dosing or adverse event data are currently available on the use of ivonescimab in patients \<18 years of age, children are excluded from this study. * ECOG performance status ≤1 (Karnofsky ≥60%,). * Patients must have adequate organ and marrow function as defined below (see Schedule of Activities) : Absolute neutrophil count ≥1,500/mcL Platelets ≥100,000/mcL Hemoglobin ≥ 9.0 g/dL Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). For patients with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤3 × ULN AST(SGOT)/ALT(SGPT) ≤2.5 × institutional ULN. For patients with liver metastases, AST and ALT ≤ 5 × ULN. Creatinine clearance (CrCl) ≥ 50 mL/min using the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) value ≥50 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation Urine protein \< 2+ or 24 hour urine protein quantification \< 1.0 g Coagulation Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 x ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy, or prophylactic coagulation). Patients receiving therapeutic anti-coagulation should be on a stable dose. * For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. Patients with active hepatitis B are required to have stable or declining levels of hepatitis B DNA by polymerase chain reaction (PCR) on appropriate anti-viral therapy with acceptable tolerability for one month prior to enrollment . * Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. * Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression for at least 3 months. * Patients with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen per PI are eligible for this trial. * Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class NYHA classification 2B or better. * The effects of ivonescimab on the developing human fetus are unknown. For this reason and because anti-PD-1 and anti-VEGFA agents have the potential to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation up to 120 days after last dose of ivonescimab. (Refer to Pregnancy Assessment Policy MD Anderson Institutional Policy # CLN1114). This includes all female patients, between the onset of menses (as early as 8 years of age) and 55 years unless the patient presents with an applicable exclusionary factor which may be one of the following: * Postmenopausal (no menses in greater than or equal to 12 consecutive months). * History of hysterectomy or bilateral salpingo-oophorectomy. * Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). * History of bilateral tubal ligation or another surgical sterilization procedure. * Approved methods of birth control are as follows: Hormonal contraception (i.e. birth control pills, injection, implant, transdermal patch, vaginal ring), Intrauterine device (IUD), Tubal Ligation or hysterectomy, Subject/Partner post vasectomy, Implantable or injectable contraceptives, and condoms plus spermicide. Not engaging in sexual activity for the total duration of the trial and the drug washout period is an acceptable practice; however periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of birth control. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. * 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 120 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 120 days after the last dose of ivonescimab. * Ability to understand and the willingness to sign a written informed consent document. * Consent to MD Anderson companion laboratory protocol 2014-0938 for correlative analyses of biopsies obtained in this trial. Exclusion Criteria: * Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. * Patients who have not recovered from adverse events due to prior anti-cancer therapy (residual toxicities that are \> Grade 2 by CTCAE v 5.0) with the exception of alopecia. * Patients who are receiving any other investigational agents. * Patients who have received prior immune checkpoint inhibitors (anti-PD-1 or anti-PD-L1 drugs). * Symptomatic CNS metastases, CNS metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to enrollment, potential need for CNS radiation within the first cycle, or leptomeningeal disease. Note: Patients must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone ≤ 10 mg daily or equivalent). * Active autoimmune or lung disease requiring systemic therapy (eg, with disease modifying drugs, prednisone \>10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to enrollment, however the following will be allowed: 1. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted. 2. Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted * Current use of systemic corticosteroids (\>10 mg daily prednisone or equivalent) * Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies * History of allergic reactions attributed to compounds of similar chemical or biologic composition to ivonescimab (immune checkpoint inhibition antibodies, antiangiogenic antibodies). * Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial. * Has pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE v5.0 * Uncontrolled pleural effusions, pericardial effusions, or ascites that is clinically symptomatic Note: Patients managed with indwelling catheters (eg, PleurX) are allowed * History of non-infectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease * Patients with psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant women are excluded from this study. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ivonescimab, breastfeeding should be discontinued if the mother is treated with ivonescimab. These potential risks may also apply to other agents used in this study. * History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to enrollment, including but not limited to: * Gastrointestinal bleeding * Hemoptysis (defined as coughing up ≥ 0.5 teaspoon of fresh blood or small blood clots) Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed. * Nasal bleeding /epistaxis (bloody nasal discharge is allowed) * Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to enrollment is not allowed. The use of full-dose anticoagulants is permitted as long as the international normalized ratio (INR) or activated partial thromboplastin time (aPTT) is within therapeutic limits according to the medical standard of the enrolling institution. * Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea) * Current hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy * Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade 2) or unstable vascular disease (eg, aortic aneurysm at risk of rupture, Moyamoya disease) that required hospitalization within 12 months prior to enrollment, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia). * Patients with acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before enrollment. * Major surgical procedures or serious trauma within 4 weeks prior to enrollment or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to enrollment. * Patients with a history of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to enrollment. * Patients with a history of esophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before enrollment. * Patients with a history of arterial thromboembolic event, venous thromboembolic event of Grade 3 and above as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to enrollment. * Imaging during the 28-day screening period shows that the patient has: * Radiologically documented evidence of major blood vessel invasion or encasement by cancer * Radiographic evidence of intratumor cavitation * Live vaccine or live attenuated vaccine within 4 weeks prior to planned enrollment, or if scheduled to receive a live vaccine or live attenuated vaccine during the study period. Inactivated vaccines are permitted. * Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation * Severe infection within 4 weeks prior to enrollment, including but not limited to comorbidities requiring hospitalization, sepsis, or severe pneumonia; active infection (as determined by the investigator) requiring systemic anti-infective therapy within 2 weeks prior to enrollment (excluding antiviral therapy for hepatitis B or C). * History or current evidence of any condition (medical \[including adverse events from prior anticancer therapy, disorders secondary to tumor\], surgical or psychiatric \[including substance abuse\]), or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, might lead to higher medical risk and/or is not in the best interest of the patient to participate, in the opinion of the treating investigator