A Phase 1 Study to Evaluate MEDI6383 Alone and in Combination With MEDI4736 in Adult Subjects With Select Advanced Solid Tumors

Inclusion Criteria: 1. Male and female subjects; age ≥ 18 2. Written informed consent must be obtained 3. Subjects must meet the following criteria: 1. Have recurrent or metastatic solid tumors 2. Must have received and have progressed, are refractory, or are intolerant to standard therapy appropriate for the specific tumor type. Subjects should not have received more than 5 prior lines of therapy for recurrent or metastatic disease including both standards of care and investigational therapies 4. Subjects must have at least 1 lesion 5. Subjects must consent to provide archived tumor specimens and / or tumor biopsy for correlative biomarker studies. 6. Eastern Cooperative Oncology Group performance score of 0 or 1 7. In the opinion of the invesgator likely to complete ≥ 8 weeks of treatment. 8. Adequate organ function as determined by: i. Absolute neutrophil count ≥ 1.5 x 109/L (1,500/mm3) ii.Platelet count ≥ 100 x 109/L (100,000/mm3) iii.Hemoglobin ≥ 9.0 g/dL within first 2 weeks prior to first dose of investigational product iv.Calculated creatinine clearance\* (CrCl) or 24 hour urine CrCl \> 50 mL/min v.Total bilirubin ≤ 1.5× ULN; for subjects with documented/suspected Gilbert's disease, bilirubin ≤ 3× ULN vi.Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5× ULN vii.Serum Electrolytes within normal limits 9. Females of childbearing potential who are sexually active with a nonsterilized male partner must use 2 methods of highly effective contraception from screening, and must agree to continue using such precautions for 90 days after the final dose of investigational product; 10) Nonsterilized males who are sexually active with a female partner of childbearing potential must use a highly effective method of contraception from Day 1 through 90 days after receipt of the final dose of investigational product Exclusion Criteria: 1. Prior treatment with TNFRSF agonists including OX40, CD27, CD137 (4-1BB), CD357 (GITR) . 2. Subjects who have received prior therapy with regimens containing CTLA-4, PDL-1, or PD-1 antagonists are NOT permitted to enroll unless all of the following apply: * Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy * All AEs while receiving prior immunotherapy must have resolved to ≤ Grade 1 or baseline prior to screening for this study. 3. Must not have experienced a ≥ Grade 3 AE or neurologic or ocular AE of any grade while receiving prior immunotherapy 4. History of severe allergic reactions to any unknown allergens or any components of the study drug formulations 5. Active or prior documented autoimmune disease within the past 2 years. 6. Untreated central nervous system metastatic disease l 7. Concurrent enrollment in another clinical study, unless it is an observational (non interventional) clinical study or the follow-up period of an interventional study 8. Receipt of anticancer therapy within 28 days prior to the first dose of Investigational Product 9. Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer treatment. 10. Unresolved toxicities from prior anticancer therapy 11. Systemic anticoagulation or daily aspirin dose exceeding 325 mg per day 12. Current or prior use of immunosuppressive medication within 14 days prior to the first dose of MEDI6383. ) 13. History of primary immunodeficiency, solid organ transplantation, or tuberculosis 14. True positive test results for human immunodeficiency virus (HIV) or hepatitis B or C 15. Receipt of live, attenuated vaccine within 28 days prior to the first dose of investigational products ) 16. Pregnant or breastfeeding women 17. Major surgery (as defined by the investigator) within 4 weeks prior to first dose of MEDI6383 or still recovering from prior surgery. Local surgery of isolated lesions for palliative intent is acceptable 18. Other invasive malignancy within 2 years \-