Phase 1b/2 Study of Combination 177Lu Girentuximab Plus Cabozantinib and Nivolumab in Treatment naïve Patients With Advanced Clear Cell RCC

Exclusion Criteria

• •1. Has received treatment with any frontline systemic therapy for metastatic RCC
• •2. Has a history of leptomeningeal disease or spinal cord compression
• •3. Has a history of autoimmune disease requiring active therapy
• •4. Has a history of brain metastases except:
• •1. Patients may be enrolled if they have treated brain metastases with no evidence of progression or hemorrhage after therapy for brain metastases (e.g. radiation therapy, surgery, radiosurgery) AND
• •2. Patients may be enrolled if they do not require ongoing treatment with dexamethasone or anti-epileptic drugs
• •6. Has uncontrolled or poorly controlled hypertension, as defined by a sustained blood pressure (BP) \> 140/90 with or without antihypertensive treatment
• •7. Has had any major cardiovascular event within 6 months prior to study drug administration including but not limited to myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, pulmonary embolism, clinically significant ventricular arrhythmias (e.g. sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes) or New York Heart Association Class III or IV heart failure
• •8. Has any other clinically significant cardiac, respiratory, or other medical or psychiatric condition that might interfere with participation in the trial or interfere with the interpretation of trial results, in the opinion of the investigator or medical monitor
• •9. Has an active infection requiring systemic treatment
• •10. Is participating in another therapeutic clinical trial
• •11. Is receiving chronic concomitant treatment with strong CYP3A4 inducers or CYP3A4 inhibitors
• •12. Has manifestations of malabsorption due to prior gastrointestinal (GI) surgery or GI disease
• •13. Has GI disorders including those associated with a high risk of perforation or fistula formation:
• •1. Tumors invading the GI-tract, active peptic ulcer disease, inflammatory bowel disease, diverticulitis, cholecystitis, symptomatic cholangitis or appendicitis, acute pancreatitis or acute obstruction of the pancreatic or biliary duct, or gastric outlet obstruction
• •2. Abdominal fistula, GI perforation, bowel obstruction, or intra-abdominal abscess within 6 months before administration of the first dose of study treatment. Note: complete healing of an intra-abdominal abscess must be confirmed before administration of the first dose of study treatment
• •14. Has tumor invading or encasing any major blood vessels
• •15. Has other clinically significant disorders such as:
• •1. Serious non-healing wound/ulcer/bone fracture
• •2. Moderate to severe hepatic impairment (Child-Pugh B or C).
• •3. Requirement for hemodialysis or peritoneal dialysis
• •4. History of solid organ transplantation
• •17. Has a prior or concomitant invasive malignancy other than RCC with the exception of adequately treated basal or squamous cell carcinoma of the skin, cervical carcinoma in situ or any other malignancy from which the patient has remained disease free for more than 2 years.