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.

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.

What this study is about