STOMP OUT: A Phase 2 Study To Evaluate The Effects Of Ivonescimab In Patients With Unresectable/Metastatic Adrenocortical Carcinoma (ACC) Or Unresectable Pheochromocytoma/Paraganglioma (PPGL)

Eligibility Criteria 1. 18 years of age or older. Because no dosing or adverse event data are currently available on the use of Ivonescimab in participants \<18 years of age, children are excluded from this study. 2. Histological confirmation of ACC or PPGL. Histological confirmation of ACC based on either: i). Weiss Score of ≥ 3 in participants who had earlier surgical resection (Lin-Weiss-Bisceglia system will be used for oncocytic ACC) OR ii). biopsy results compatible with ACC in the context of clinical setting highly suggestive of ACC (adrenal mass \> 4 cm invading surrounding organs or associated with distant metastases). 3. Locally advanced or metastatic disease not amenable to surgery 4. Participants must have measurable disease per RECIST v1.1. Participants must have a visceral or soft tissue metastasis measuring at least 10mm by the longest axis with CT scan or MRI. Nodal metastases must measure at least 15mm by short axis. Bone metastases require a soft tissue component with the longest axis being at least 10 mm to be considered measurable. 5. Progressive disease per RECIST v1.1 as determined by the investigator within the 12 months preceding study enrollment 6. Assessment of all known disease sites, eg, by computerized tomography (CT) scan, magnetic resonance imaging (MRI), bone scan as appropriate, and/or FDG-PET scan within 28 days before the first dose of ivonescimab 7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. 8. Life expectancy of at least 3 months 9. Organ and marrow function and laboratory values as follows within 48 hours prior to the first dose of ivonescimab: 1. Absolute neutrophil count (ANC) ≥ 1500/mm3 2. Platelets ≥ 100,000/mm3 3. Hemoglobin ≥ 9 g/dL, and no blood transfusion or erythropoietin stimulating agent is allowed within 7 days of enrollment. 4. 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 participants who are not on therapeutic anti-coagulation. Participants receiving therapeutic anticoagulation should be on a stable dose 5. Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); For participants with liver metastases or confirmed/suspected Gilbert syndrome, TBIL ≤3 × ULN 6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; For participants with liver metastases, AST and ALT ≤ 5 × ULN 7. Serum albumin ≥ 2.8 g/dl 8. Serum creatinine ≤ 1.5 ´ ULN or creatinine clearance (CrCl) ≥ 50 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used: Male: CrCl (mL/min) = (140 - age) × wt (kg) / (serum creatinine × 72) Female: Multiply above result by 0.85 9. Urine protein/creatinine ratio (UPCR) ≤ 1 10. Capable of understanding and complying with the protocol requirements and has signed the informed consent document. 11. Female participants of childbearing potential 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. 12. Female participants of childbearing potential must have a negative pregnancy test at screening. Female of childbearing potential include women who have experienced menarche and who have not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or are not postmenopausal. Postmenopausal is defined as amenorrhea ≥ 12 consecutive months. Note: females who have been amenorrheic for 12 or more months are still considered to be of childbearing potential if the amenorrhea is possibly due to prior chemotherapy, antiestrogens, ovarian suppression or any other reversible reason. 13. Female participant 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 daysafter the last dose of the ivonescimab. 14. Unsterilized male participants 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 participants 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 A subject who meets any of the following criteria is ineligible for the study: 1. Received cytotoxic chemotherapy (including investigational cytotoxic chemotherapy) or biologic agents (e.g., cytokines or antibodies) within 4 weeks of the start of the previous cycle or had received previous targeted therapy including small molecular tyrosine kinase inhibitors such as belzutifan, cabozantinib or lenvatinib within 2 weeks before the first dose of study treatment. 2. Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before the first dose of study treatment. Subjects with clinically relevant ongoing complications from prior radiation therapy are not eligible. 3. 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. 4. Active autoimmune or lung disease requiring systemic therapy (e.g., with disease modifying drugs, prednisone \>10 mg daily or equivalent, immunosuppressant therapy) within 2 years prior to first dose of study treatment however the following will be allowed: 1. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for thyroid, adrenal or pituitary insufficiency) is permitted. 2. Intermittent use of bronchodilators, inhaled corticosteroids, or local corticosteroid injections is permitted 3. Psoriasis requiring topical treatment only, vitiligo, history of Hashimoto's thyroiditis, Grave's disease, history of radiographic diagnosis of rheumatoid arthritis without active therapy is allowed. 5. Received radionuclide treatment (i.e. I 131 meta-iodo- benzyl guanidine) within 3 months of the first dose of study treatment 6. Receipt of any other type of investigational agent within 28 days before the first dose of study treatment. 7. The subject has not recovered to baseline or CTCAE ≤ Grade 1 from toxicity due to all prior therapies except alopecia and other non-clinically significant AEs. 8. Symptomatic CNS metastases, CNS metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to randomization, potential need for CNS radiation within the first cycle, or leptomeningeal disease Note: Participants must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone ≤ 10 mg daily or equivalent). 9. Live vaccine or live attenuated vaccine within 4 weeks prior to planned first dose of study treatment , or if scheduled to receive a live vaccine or live attenuated vaccine during the study period. Inactivated vaccines are permitted. 10. 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 randomization (excluding antiviral therapy for hepatitis B or C) 11. Has pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE version 6.0 12. Uncontrolled pleural effusions, pericardial effusions, or ascites that is clinically symptomatic Note: Participants managed with indwelling catheters (eg, PleurX) are allowed. 13. History of non-infectious pneumonia requiring systemic corticosteroids, or current interstitial lung disease 14. Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea) 15. Known history of human immunodeficiency virus (HIV) whose viral load is not controlled. 16. Current use of systemic corticosteroids (\>10 mg daily prednisone or equivalent) 17. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation 18. Participants 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 randomization. All participants with active hepatitis C (hepatitis C virus \[HCV\] antibody positive with HCV RNA levels above the lower limit of detection) are excluded. 19. Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies 20. 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 participant to participate, in the opinion of the treating investigator 21. Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to randomization 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 22. The subject has experienced any of the following: 1. clinically-significant gastrointestinal bleeding within 6 months before the first dose of study treatment 2. hemoptysis of ≥ 0.5 teaspoon (2.5ml) of red blood within 3 months before the first dose of study treatment 3. any other signs indicative of pulmonary hemorrhage within 3 months before the first dose of study treatment 23. Radiographic evidence of cavitating pulmonary lesion(s) 24. Tumor invading or encasing any major blood vessels with the exception of tumor thrombus associated with the primary tumor or located within the renal/adrenal vein or vena cava. 25. Evidence of tumor invading the GI tract (esophagus, stomach, small or large bowel, rectum or anus), or any evidence of endotracheal or endobronchial tumor within 28 days before the first dose of ivonescimab 26. Uncontrolled, significant intercurrent or recent illness including, but not limited to, the following conditions: a. Cardiovascular disorders including i. History of any grade arterial thromboembolic event, Grade 3 and above venous thromboembolic event, as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 6.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to first dose of study treatment ii. Congestive heart failure (CHF): New York Heart Association (NYHA) Class II, Class III or Class IV at the time of screening iii. Concurrent uncontrolled hypertension defined as sustained BP \> 150 mm Hg systolic, or \> 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment iv. Any history of congenital long QT syndrome v. Any of the following within 12 months before the first dose of study treatment: * unstable angina pectoris * clinically-significant cardiac arrhythmias * stroke (including TIA, or other ischemic event) * myocardial infarction * CTCAE grade 3 or higher venous thromboembolism * Unstable vascular disease (e.g. aortic aneurysm at risk of rupture, Moyamoya disease that required hospitalization) b. Gastrointestinal disorders particularly those associated with a high risk of perforation or fistula formation including: i. Any of the following within 6 months before the first dose of study treatment * intra-abdominal tumor/metastases invading GI mucosa * active peptic ulcer disease; participants must be completely recovered * inflammatory bowel disease (including ulcerative colitis and Crohn's disease), diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis; participants must be completely recovered from these conditions * abdominal fistula * gastrointestinal perforation * bowel obstruction or gastric outlet obstruction * intra-abdominal abscess. Note: Complete resolution of an intra-abdominal abscess must be confirmed prior to initiating treatment with ivonescimab even if the abscess occurred more than 6 months before the first dose of study treatment. c. Other disorders associated with a high risk of fistula formation including PEG tube placement within 3 months before the first dose of study therapy 27. Pregnant or breastfeeding. 28. A previously identified allergy or hypersensitivity to components of the study treatment formulation. 29. Unable or unwilling to abide by the study protocol or cooperate fully with the investigator or designee. 30. Evidence within 2 years of the start of study treatment of another malignancy which required systemic treatment except for cured nonmelanoma skin cancer, cured in situ cervical carcinoma, or evidence of localized adenocarcinoma of the prostate Gleason score 6 (3+3) or 7 (3+4 or 4+3) undergoing active surveillance. 31. Any other severe acute or chronic medical or psychiatric condition or laboratory abnormality which, in the judgment of the investigator, would have made the participant inappropriate for entry into this study.