Naptumomab Estafenatox in Combination With Durvalumab in Subjects With Selected Advanced or Metastatic Solid Tumor, Including a Cohort Expansion in Esophageal Cancer.

Subjects must meet all of the following criteria to participate in this study: 1. Adult at least 18 years of age 2. For the Dose-escalation and MTD Expansion Cohorts: Histologically and/or cytologically confirmed solid tumor from the following list, that is metastatic/advanced, and for which no curative therapy exists: 1. Pancreatic adenocarcinoma 2. High-grade serous ovarian cancer 3. Cervical squamous cell carcinoma 4. Prostate cancer 5. ER+/HER2- or triple-negative breast cancer 6. NSCLC including driver mutation positive. 7. Mesothelioma 8. Renal cell carcinoma 9. Bladder/urothelial cancer 10. Head and neck squamous cell carcinoma 11. Melanoma 12. Hepatocellular carcinoma 13. Endometrial cancer 14. MTD Expansion Cohort only: 5T4-positive colorectal cancer and 5T4 positive GE cancer 3. For the Esophageal Expansion Cohort: Subjects must have histologically confirmed locally advanced or metastatic ESCC or AC of the esophagus or GEJ (Siewert type 1). 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. All patients must provide signed informed consent prior to any study specific procedures that are not part of standard medical care. 6. In the MTD Expansion Cohort only, an archival or fresh biopsy will be acceptable at baseline. A second biopsy on Cycle 2 Day 4 is optional for patients who provided a fresh biopsy at baseline or have a tumor sample available from up to 3 months prior to study entry. Patients enrolled in the MTD expansion cohort after prior exposure to a CPI should have a baseline biopsy obtained after completion of the last prior CPI therapy. For the Esophageal Cohort Expansion: Subjects must have adequate tumor tissue (as defined in the laboratory manual) for biomarker analysis. If the archival tissue was taken \> 1 year prior to screening into the trial, a fresh biopsy is required. Patients enrolled in Group 2 should have a baseline biopsy obtained after completion of the last prior CPI therapy. Bone samples, fine needle aspirates, brushings, cell pellets, and lavage are not acceptable samples. 7. Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 28 days prior to Cycle 1 Day 1 (first NAP treatment day) 1. Dose-escalation part: patients do not need to have measurable disease by RECIST 1.1 2. MTD Dose Expansion: patients must have measurable disease by iRECIST/RECIST 1.1. Previously irradiated lesions may be considered measurable if there has been demonstrated progression in these lesions. 3. For the Esophageal Cohort Expansion: Patients must have measurable disease per iRECIST/RECIST version 1.1 by local investigator/ radiology assessment, unresectable based on documented opinion, or refusing surgery. 8. Previous therapy: a. Dose Escalation and MTD Expansion: i. All patients must have received at least 1 standard systemic cancer therapy for their tumor type and progressed following their most recent regimen. There is no limit to the number of prior cytotoxic regimens received. ii. Treatment-naïve patients will be eligible only if they refused standard treatment. iii. Patients with prior anti-PD-1, anti PD-L1, or anti-CTLA4 therapy are eligible if they have received such therapy for a minimum of 6 months and if they have documented progression of their disease on or off such therapy. b. Esophageal Cohort Expansion: i. Group 1 - no prior CPI: Subjects with only ESCC who may have received up to 1 prior chemotherapy as a line for metastatic disease or up to 2 prior chemotherapies if they also received neoadjuvant/adjuvant systemic therapy, but no prior CPI. If subjects received prior chemotherapy for metastatic disease, they should have documented radiographic or clinical progression. ii. Group 2 - prior CPI: Subjects with either ESCC or AC of the esophagus or GEJ (Siewert type 1) who must not have had more than 2 prior lines of therapy. Patients will be allowed to have up to 2 prior regimens for metastatic disease, or up to 3 prior therapies if they also received neoadjuvant/adjuvant systemic therapy. Subjects are eligible provided that they have received CPI therapy for at least 9 weeks, provided that they have documented progression of their disease on such therapy, and provided that the prior CPI was not discontinued for toxicity. No more than 1 prior CPI treatment is allowed (prior combination of anti-PD-\[L\]1 and anti-CTLA-4 is acceptable). Subjects with AC that is HER 2/neu negative. 9. Subjects with known, suspected, or documented parenchymal brain metastases, unless treated with surgery and/or radiation, with the subject neurologically stable and off pharmacologic doses of systemic glucocorticoids (equivalent to \< 10 mg/day of prednisone); subjects with leptomeningeal metastases are not eligible. Subjects should have completed brain radiation at least 14 days before start of obinutuzumab treatment. 10. Prior treatment with chemotherapy or other systemic antineoplastic therapy within 21 days; prior experimental therapy within 21 days or 5 half-lives, whichever is shorter. 11. The use of immunosuppressive agents within 28 days of obinutuzumab administration including, but not limited to, cyclosporine, mycophenolate, azathioprine, methotrexate, adalimumab, infliximab, vedolizumab, tofacitinib, dupilumab, rituximab, etc. Pharmacologic doses of glucocorticoids defined as glucocorticoid equivalents of \> 10 mg/day of prednisone (except when required for study medications or used prior to administration of radiographic contrast material in subjects with allergies) are not acceptable within 14 days of obinutuzumab administration. Subjects are permitted to receive topical, intranasal, inhalational, and intra ocular glucocorticoids. 12. Adequate hematologic and organ function: 1. White blood cells (WBC) ≥ 3000/μL 2. Absolute neutrophil count (ANC) ≥ 1500/μL 3. Platelets ≥ 100,000/μL 4. Hemoglobin ≥ 9 g/dL 5. Serum creatinine ≤ 1.5 mg/dL or calculated creatinine clearance (CrCL) \> 40 mL/sec by Cockcroft-Gault (using actual body weight) 6. Aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) ≤ 2.5 × ULN (for patients with known liver involvement AST and ALT ≤ 5 × ULN); bilirubin ≤ 1.5 mg/dL (unless diagnosed with Gilbert's syndrome) 7. International normalized ratio (INR) or prothrombin time (PT) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Subjects on anticoagulant therapy should be discussed with the Medical Monitor. 13. Patients must be willing and able to comply with scheduled visits, drug administration plan, hospitalization for treatment (if needed) and scheduled follow-up visits and examinations as outlined in the protocol, including procedures undertaken to perform fresh tumor biopsies if needed. 14. Must have a life expectancy of at least 3 months. 15. Negative pregnancy test (serum) for women of childbearing potential. 16. Female participants must be ≥ 1 year post-menopausal, surgically sterile, or using 1 highly effective form of birth control (a highly effective method of contraception is defined as one that can achieve a failure rate of less than 1% per year when used consistently and correctly.) Women of childbearing potential must agree to use 1 highly effective method of birth control. They should have been stable on their chosen method of birth control for a minimum of 3 months before entering the study until 90 days after the last dose of NAP + durvalumab combination therapy or durvalumab monotherapy. Non sterilized male partners of a female subject of childbearing potential must use a male condom plus spermicide throughout this period. 17. Male participants who intend to be sexually active with a female partner of childbearing potential must be surgically sterile or using an acceptable method of contraception from the time of Screening throughout the total duration of the study and until 90 days after the last dose of NAP + durvalumab combination therapy or durvalumab monotherapy to prevent pregnancy in a partner. Male participants must not donate or bank sperm during this same time period.