Phase 2 Trial of Zanzalintinib and Pembrolizumab in Select Subtypes of Advanced/Metastatic Soft-tissue Sarcoma

Eligibility Criteria * Participants must have histologically or cytologically confirmed undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), high grade pleomorphic (HGPS) or undifferentiated sarcoma (HGUS). * Participant ≥ 18 years of age. Because no dosing or adverse event data are currently available on the use of zanzalintinib in combination with pembrolizumab in participants \<18 years of age, children are excluded from this study. * ECOG performance status ≤2 (Karnofsky ≥60%). * Participants must have measurable disease, 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, or calipers by clinical exam. * At least 4 weeks since prior chemotherapy. * At least 2 weeks since radiation therapy for bone metastases, any other radiation therapy within 4 weeks before first dose of study treatment. At least 6 weeks since systemic treatment with radionuclides before first dose of study treatment. * Participants must have adequate organ and marrow function as defined below within 14 days before first dose of study treatment: absolute neutrophil count ≥1,500/mcL without granulocyte colony-stimulating factor support within 2 weeks of screening laboratory sample collection. platelets ≥100,000/mcL without transfusion within 2 weeks of screening laboratory sample collection. hemoglobin ≥ 9 g/dL (≥ 90 g/L) without transfusion within 2 weeks prior to screening laboratory sample collection. international normalized ratio (INR) ≤ 1.5 and activated partial thromboplastin time (aPTT) ≤ 1.2 x upper limit of normal (ULN ). total bilirubin ≤ 1.5 x institutional ULN AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN Alkaline phosphatase (ALP) ≤3 × institutional ULN, . For subjects with documented bone metastasis ALP ≤ 5 x ULN. creatinine ≤ 1.5 x institutional ULN or calculated creatinine clearance ≥ 40 mL/min (≥ 0.67 mL/sec) using the Cockcroft Gault equation. Urine protein-to-creatinine ratio (UPCR) ≤ 1 mg/mg (≤ 113.2 mg/mmol) * For participants with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated. * Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load. * Participants 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 4 weeks. Note: Participants must have stopped corticosteroids or be on physiologic corticosteroid replacement therapy (prednisone ≤ 10 mg daily or equivalent). * Participants with new or progressive brain metastases (active brain metastases) or leptomeningeal disease are eligible if the treating physician determines that immediate CNS specific treatment is not required and is unlikely to be required during the first three cycles of therapy. * 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. * Participants 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, participants should be class 2B or better. * The effects of zanzalintinib and pembrolizumab on the developing human fetus are unknown. For this reason, 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. (Refer to Pregnancy Assessment Policy 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: o Postmenopausal (no menses in greater than or equal to 12 consecutive months). o History of hysterectomy or bilateral salpingo-oophorectomy. o Ovarian failure (Follicle Stimulating Hormone and Estradiol in menopausal range, who have received Whole Pelvic Radiation Therapy). o History of bilateral tubal ligation or another surgical sterilization procedure. o Note: Documentation may include review of medical records, medical examination, or medical history interview by study site staff. * Females must not be pregnant. * 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. * Women of childbearing potential must comply for the duration of study participation and through 186 days after the last dose of zanzalintinib and 180 days after the last dose of pembrolizumab, whichever date is later. Men must comply for the duration of study participation and through 96 days after the last dose of zanzalintinib or 96 days of pembrolizumab, whichever date is later. * Capable of understanding and compl…

Reproduced word-for-word from the public registry record — the study team can answer questions about it.