Angiosarcoma Clinical Trials

• 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.