Pilot Study of Ivonescimab in Advanced/Metastatic Cutaneous Angiosarcoma

This is a pilot study evaluating the efficacy and safety of ivonescimab in subjects with advanced or metastatic cutaneous angiosarcoma who have previously been treated with taxane-based chemotherapy.

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 \ 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