A Two-arm, Single Center Phase 1b Trial of Bavituximab Plus Ipilimumab in Advanced Melanoma Patients

Inclusion Criteria: 1. Histologic diagnosis of unresectable or metastatic melanoma. For unknown primary disease, diagnosis of metastatic disease by cytology FNA (Fine Needle Aspiration) is not acceptable. 2. Any number of prior systemic therapeutic regimens including chemotherapy, pathway inhibitors, biochemotherapy, investigational agents, and immunotherapies other than ipilimumab or bavituximab. 3. Subjects must have measurable disease as defined by irRC. All sites must be evaluated within 4 weeks prior to beginning therapy. 4. Age ≥ 18 years. 5. Performance status ECOG (Eastern Cooperative Oncology Group) 0-2. 6. Adequate organ and marrow function as defined below: * leukocytes ≥ 2,000/mcL (Microliter) * absolute neutrophil count ≥ 1,500/mcL * platelets ≥ 100,000/mcl * total bilirubin \< 3X (times) institutional upper limit of normal * AST (Aspartate Aminotransferase) (SGOT)/ALT (Alanine Aminotransferase)(SPGT) ≤ 2.5 X institutional upper limit of normal * creatinine \< 3X institutional upper limit of normal * hemoglobin \>8g/dL 7. Ability to understand and the willingness to sign a written informed consent. 8. Subjects must be willing to undergo tumor biopsy pretreatment and at weeks 3 and 15. 9. 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, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria: has not undergone a hysterectomy or bilateral oophorectomy; or has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months). Exclusion Criteria: 1. No concomitant therapy with any of the following: IL2 (Interleukin 2), interferon, or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigational therapies; or chronic use of systemic corticosteroids; all such therapies must have been discontinued \>4weeks. 2. No infection with HIV and no active infection with hepatitis B and no active or chronic infection with hepatitis C. Due to the mechanism of action of ipilimumab, activity and side effects in an immune compromised patient are unknown. 3. Subjects with active CNS (Central nervous system) disease are excluded. Patient with brain metastases previously treated with surgery or stereotactic radiosurgery and with confirmed SD for \>8 weeks are allowed. 4. Subjects are excluded if they have a history of any other malignancy from which the patient has been disease-free for less than 2 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix. 5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. 6. Subjects must not be pregnant or nursing. 7. Any concurrent medical condition requiring the use of systemic steroids is not permitted (the use of inhaled or topic steroids is permitted). 8. Subjects are excluded for receiving any non-oncology vaccine therapy used for prevention of infectious diseases for up to 4 weeks (28 days) prior to or after any dose of ipilimumab. 9. Subjects are excluded if they have a history of prior treatment with ipilimumab, CD137 agonist , CTLA-4 inhibitor (Cytotoxic T-Lymphocyte Antigen 4) or agonist or bavituximab. 10. Patients are excluded if they have a history of autoimmune disease except controlled and stable autoimmune thyroiditis. The excluded autoimmune diseases include acute disseminated encephalomyelitis, Addison's disease, alopecia universalis, ankylosing spondylitis, antiphospholipid antibody syndrome, aplastic anemia, asthma, autoimmune hemolytic anemia, autoimmune hepatitis, autoimmune hypoparathyroidism, autoimmune hypophysitis, autoimmune myocarditis, autoimmune oophoritis, autoimmune orchitis, autoimmune thrombocytopenic purpura, Behcet's disease, bullous pemphigoid, celiac disease, chronic fatigue syndrome, chronic inflammatory demyelinating polyneuropathy, Churg-Strauss syndrome, Crohn's disease, dermatomyositis, dysautonomia, eczema, epidermolysis bullossa acquisita, gestational pemphigoid, giant cell arteritis, Goodpasture's syndrome, Graves' disease, Guillain-Barre syndrome, Hashimoto's disease-except as noted above, IgA nephropathy (Berger's disease), inflammatory bowel disease, interstitial cystitis, Kawasaki's disease, Lambert-Eaton myasthenia syndrome, lupus erythematosis, chronic Lyme disease, Meniere's syndrome, Mooren's ulcer, Morphea, multiple sclerosis, myasthenia gravis, neuromyotonia, opsoclonus myoclonus syndrome, optic neuritis, Ord's thyroiditis, pemphigus, pernicious anemia, polyarteritis nodosa, polyarthritis, polyglandular autoimmune syndrome, primary biliary cirrhosis, psoriasis, Reiter's syndrome, rheumatoid arthritis, sarcoidosis, Sjogren's syndrome, Stiff-Person syndrome, Takayasu's arteritis, ulcerative colitis, Vogt- Kovanagi-Harada disease, vulvodynia, and Wegener's granulomatosis. 11. Subjects are excluded with history of thromboembolic events, clinically significant bleeding-gross hematuria, hemoptysis, or gastrointestinal bleeding, history of bleeding diathesis or hypercoagulable state, ongoing therapy with anticoagulants or non-steroidal anti-inflammatory drugs, or prior exposure to chimeric antibodies.