A Phase II Study of Ivonescimab Combined With Intraperitoneal Paclitaxel in Patients With High-Grade Metastatic Appendiceal Adenocarcinoma (AA)

Inclusion Criteria * Age 18 years and above. There will be no upper age restriction * ECOG performance status 0-2 * Participants must have histologically confirmed diagnosis of unresectable metastatic AA. The determination of appendiceal origin may rely on pathologic features combined with clinical or radiographic evidence in the event that the appendix remains in situ. * Participants will have undergone no more than two prior lines of systemic therapy. The last dose of systemic therapy will have been no less than 2 weeks prior to initiation of therapy. * Participants must have adequate nutrition and normal bowel motility and function as evidenced by albumin \> 3.0 and no history of intestinal bypass or diverting enterostomy. * Demonstrate adequate organ function as determined by the following requirements: o Hematology * No use of any blood components and cell growth factor supportive therapy within 7 days prior to initiation of study treatment * Absolute neutrophil count (ANC) ≥ 1,500/mm3 (ANC ≥ 1000/mm3 for African American participants) * Platelet count ≥ 100 × 109/L (100,000/mm3) * Hemoglobin ≥ 9.0 g/dL. o Kidney: * 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 (adjustment by body surface area \[BSA\] is not required for eGFR). \*CrCL or eGFR can be determined using the calculator from the National Kidney Foundation website (www.kidney.org). * Urine protein \< 2+ or 24-hour urine protein quantification \< 1.0 g o Liver: * Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); for participants with confirmed/suspected Gilbert syndrome, TBIL ≤3 x ULN * Aspartate transaminase (AST) and alanine aminotransferase (ALT) ≤ 2.5 ULN * Coagulation: prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 × ULN, and partial thromboplastic 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 anti-coagulation should be on a stable dose * The effects of PTX and Ivonescimab on the developing human fetus are unknown. Taxane agents are known to be teratogenic. Additionally, based on Ivonescimab's mechanism of action, it may cause fetal harm if administered to a pregnant woman. For this reason, women of childbearing 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 until 6 months after the last dose of Ivonescimab. (Refer to Pregnancy Assessment Policy UT MD Anderson Institutional Policy # CLN1114). This includes all female participants, between the onset of menses (as early as 8 years of age) and 55 years unless the participant 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 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 6 months after last dose of Ivonescimab or chemotherapy. 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 treatment period until 6 months after last dose of Ivonescimab. * Female participants of childbearing age must have a negative serum pregnancy test result before enrollment and a negative urine pregnancy test on the day of first dose prior to dosing. * Ability to understand and the willingness to sign a written informed consent document * Participants with a prior or concurrent malignancy whose natural history or treatment does not interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Exclusion Criteria * Metastases outside the peritoneal cavity, with exception of limited metastases to the thoracic cavity and/or limited retroperitoneal lymphadenopathy * Previous surgery that would preclude safe diagnostic laparoscopy with port placement * Current presence of significant radiographic or clinical/radiographic manifestations of gastrointestinal obstruction. 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 * Recent history (within the last 30 days) of large volume ascites requiring repeated paracenteses. Large-volume ascites that has resolved with prior systemic therapies is not considered Exclusionary. * Unresolved clinically significant toxicity of greater than or equal to NCI CTCAE v. 6.0 grade 2 attributed to any prior therapies (excluding anemia, lymphopenia, alopecia, skin pigmentation). * Other prior malignancy unless the participant has undergone curative therapy with no evidence of disease recurrence within 3 years prior to enrollment. The following malignancies will be allowed without the 3-year interval after adequate treatment: basal cell or squamous cell carcinoma of skin, superficial bladder cancer, in situ cervical cancer, other in situ cancers, prostate cancer with a Gleason score ≤6 that does not need therapy or other local tumors that are considered cured * Concurrent enrollment in another clinical study, unless it is an observational, non-interventional clinical study or a follow-up period for an interventional study. * Palliative local therapy for non-target lesions and non-specific immunomodulatory therapy (such as interleukin, interferon, thymus peptide, tumor necrosis factor, etc.) within 2 weeks before the first dose. * Any prior clinically significant or active autoimmune disease requiring systemic therapy (e.g., with disease- modifying drugs, prednisone \>10 mg daily or equivalent, immunosuppressant therapy or immunomodulatory agents \[e.g., infliximab or IVIG\]) within 2 years prior to enrollment; however, replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted. * History of major diseases before enrollment, specifically: * Unstable angina, myocardial infarction, CHF (New York Heart Association \[NYHA\] classification ≥Grade 2) or unstable vascular disease (e.g., 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 (e.g., poorly controlled arrhythmias, myocardial ischemia) * History of esophageal gastric varices, severe ulcers, wounds that do not heal, fistula, intra-abdominal abscesses, or ≥ Grade 3 acute gastrointestinal bleeding within 6 months before enrollment * History of any grade arterial thromboembolic event (ATE), Grade 3 and above venous thromboembolism (VTE), as specified in NCI CTCAE6.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 12 months prior to enrollmentAcute exacerbation of chronic obstructive pulmonary disease within 4 weeks before enrollment * 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. * Severe infection within 4 weeks prior to enrolment, 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). * 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 within 3 days prior to enrollment (excluding central venous catheterization and port implantation). * 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: * Clinically significant gastrointestinal bleeding such as hematochezia of approximately 1 tablespoon or more per day or any episodes of melena or documented acute hemoglobin drop of more than 1 gm in 2 weeks prior to enrollment * 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 fulldose anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits according to the medical standard of the enrolling institution. * Poorly controlled hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy * History of non-infectious pneumonia requiring systemic corticosteroids. History of or current interstitial lung disease * Active or prior history of inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis, or chronic diarrhea) * Current use of systemic corticosteroids (\>10 mg daily prednisone or equivalent) * Participants with known active tuberculosis (TB) and suspected active TB need to be ruled out by clinical examination. * Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation. * Known history of human immunodeficiency virus (HIV) whose viral load is not controlled * Participants with active hepatitis B are required to have stable or declining levels of hepatitis B virus (HBV) DNA by polymerase chain reaction (PCR) on appropriate anti-viral therapy with acceptable tolerability for 1 month prior to enrollment. All active hepatitis C participants (hepatitis C virus \[HCV\] positive with HCV RNA levels above the lower limit of detection) are excluded. * Known hypersensitivity to any component of any of the study drugs; known history of severe hypersensitivity reactions to other monoclonal antibodies. * History or current evidence of any condition (medical \[including AEs from prior anti- cancer therapy, disorders secondary to tumor\], surgical or psychiatric \[including current substance abuse\]), or laboratory abnormality that might confound the results of the study, interfere with the participant'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 * Pregnant women are excluded from this study because both paclitaxel and Ivonescimab have potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with these agents, breastfeeding should be discontinued. * Participant is breastfeeding or plans to breastfeed during the study. * Participants with psychiatric illness/social situations that would limit compliance with study requirements