A Phase 2 Trial of Ivonescimab for Patients With Advanced, Metastatic Salivary Gland Cancers

Exclusion Criteria

• •Participant has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment) and have no evidence of new or enlarging brain metastases.
• •Concurrent administration of other cancer specific therapy or investigational agents during the course of this study is not allowed.
• •Uncontrolled intercurrent illness including but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• •Pregnant or lactating women as the effects of the investigational therapy (ivonescimab) on the developing human fetus are unknown.
• •Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer, and low- risk prostate adenocarcinoma being managed with active surveillance. A history of another separate malignancy in remission without evidence of active disease in the last 2 years is permitted.
• •Existing significant autoimmune conditions. Patients with a history of Hashimoto thyroiditis who are stable on replacement hormone therapy are not excluded. Patients cannot be on long-term (\>4 weeks) corticosteroids at doses exceeding prednisone 10 mg daily (or its equivalent).
• •Major surgical procedures or serious trauma within 4 weeks prior to starting therapy 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) are permitted.
• •History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to the start of therapy, including but not limited to:
• •* a. Gastrointestinal bleeding
• •* b. Hemoptysis (defined as coughing up ≥0.5 teaspoon of fresh blood or small blood clots). Note: transient hemoptysis associated with diagnostic bronchoscopy is allowed.
• •* c. Significant nasal bleeding/epistaxis (bloody nasal discharge is allowed)
• •* d. Need for therapeutic anticoagulant therapy within 14 days prior to the start of therapy.
• •Current hypertension with systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg after oral antihypertensive therapy.
• •History of major diseases , specifically:
• •* a. Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association \[NYHA\] classification ≥ grade 2) or vascular disease (eg, aortic aneurysm at risk of rupture) that required hospitalization within 12 months prior to randomization, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)
• •* b. 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 randomization
• •* c. 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) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to randomization
• •* d. Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before randomization
• •* e. 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 randomization
• •Imaging during the screening period shows that the patient has:
• •* a. Radiologically documented evidence of major blood vessel invasion or encasement by cancer (per the judgment of the treatment investigator)
• •* b. Radiographic evidence of intratumor cavitation (per the judgment of the treating investigator)