Study of Carotuximab (TRC105) Plus Nivolumab in Patients With Metastatic NSCLC

Exclusion Criteria

• •1. Autoimmune disease requiring treatment within the past twelve months.
• •2. Condition requiring systemic treatment with either corticosteroids
• •3. History or active interstitial lung disease
• •4. Prior therapy with T-cell therapy, including an immune checkpoint inhibitor. Patients who received prior immune checkpoint inhibitor therapy are allowed in Expansion Cohort 2 in the absence of recurrent grade 2 (except skin, endocrine and constitutional symptoms), or ≥ 3 immune-related toxicity).
• •5. Prior treatment with carotuximab
• •6. Current treatment on another therapeutic clinical trial
• •7. Receipt of systemic anticancer therapy, including investigational agents, within 28 days prior to study treatment (Note: If anticancer therapy was given within 28 days prior to starting study treatment, patients are not excluded if ≥ 5 times the elimination half-life of the drug has elapsed.)
• •8. Major surgical procedure or significant traumatic injury within 4 weeks prior to study treatment, and must have fully recovered from any such procedure; and no date of surgery (if applicable) or anticipated need for a major surgical procedure planned within the next 6 months
• •9. Chest radiotherapy ≤ 28 days, wide field radiotherapy ≤ 28 days (defined as \> 50% of volume of pelvic bones or equivalent), or limited field radiation for palliation ≤ 14 days prior to study treatment - Such patients must have recovered adequately from any side effects of such therapy.
• •10. Hypertension defined as blood pressure (BP) systolic \> 150 or diastolic \> 90 mm Hg (Note: Initiation or adjustment of antihypertensive medication prior to study entry is allowed provided that the average of 3 BP readings prior to study treatment is ≤150/90 mm Hg.)
• •11. Ascites or pericardial effusion that required intervention within 3 months prior to study treatment
• •12. History of brain involvement with cancer, spinal cord compression, or carcinomatous meningitis, or new evidence of brain or leptomeningeal disease
• •13. Angina, myocardial infarction (MI), symptomatic congestive heart failure, cerebrovascular accident, transient ischemic attack TIA), arterial embolism, pulmonary embolism, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG) within 6 months prior to study treatment
• •14. Deep venous thrombosis within 6 months prior to study treatment, unless the patient is anti-coagulated without the use of warfarin for ≥2 weeks prior to study treatment; in this situation, low molecular weight heparin is preferred
• •15. Active bleeding or pathologic condition that carries a high risk of bleeding (e.g., hereditary hemorrhagic telangiectasia)
• •16. Thrombolytic use (except to maintain IV catheters) within 10 days prior study treatment
• •17. Known active viral or nonviral hepatitis or cirrhosis
• •18. Any active infection requiring systemic treatment
• •19. History of hemorrhage or hemoptysis (\> ½ teaspoon bright red blood) within 3 months prior to study treatment
• •20. History of peptic ulcer within the past 3 months prior to study treatment, unless treated for the condition and complete resolution has been documented by esophagogastroduodenoscopy (EGD) within 28 days prior to study treatment
• •21. History of gastrointestinal perforation or fistula in the 6 months prior to study treatment, or while previously on antiangiogenic therapy, unless underlying risk has been resolved (e.g., through surgical resection or repair)
• •22. Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness
• •23. Pregnancy or breastfeeding - Female patients must be surgically sterile (i.e., ≥6 weeks following surgical bilateral oophorectomy with or without hysterectomy or tubal ligation) or be postmenopausal, or must agree to use effective contraception during the study and for 3 months following last dose of carotuximab. All female patients of reproductive potential must have a negative pregnancy test (serum or urine) within 7 days prior to study treatment. Male patients must be surgically sterile or must agree to use effective contraception during the study and for at least 180 days following last dose of study drug (carotuximab or nivolumab, whichever occurs later).
• •24. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for this study.