Safety and Efficacy of Repeat Administration of Ad/PNP and Fludarabine Phosphate in Patients With Local Head/Neck Cancer

Inclusion Criteria:

1. Provided Informed Consent

2. Age ≥ 18 years

3. Patients with histologically or cytologically confirmed diagnosis of recurrentcancer of the head and neck region for whom there is no curative treatment option.For the purposes of trial eligibility, cancers of the head and neck shall include,in addition to head and neck squamous cell carcinoma (HNSCC), cutaneous squamouscell primary sites and squamous cell carcinoma of unknown primary presenting withneck lymph nodal disease, as well as nasopharyngeal carcinoma, and salivary glandtumors.

4. All standard or approved treatment options that would provide substantive palliationmust have failed, been exhausted, or patient not eligible or willing to use them (for example neuropathy, nephropathy , or hearing loss precluding the use ofcisplatin)

5. Tumor mass (primary tumor and/or lymphadenopathy) measurable by Response EvaluationCriteria in Solid Tumors (RECIST) 1.1 and technically suitable for intratumoralinjections (otolaryngologist will determine feasibility). Patients with nodaldisease (or metastatic disease) that is needle accessible are eligible. Patientswith additional tumors (including distant metastatic disease) beyond theintratumoral injection accessible tumor(s) that are not accessible for intratumoralinjection are eligible ONLY if the patient has no other treatment option for themetastatic disease and treatment of local disease may provide the patient somebenefit or palliation.

6. Eastern Cooperative Oncology Group performance status of ≤ 2

7. In the judgment of the Investigator, the patient has recovered sufficiently from anyprevious significant therapy side effects or toxicities prior to Ad/PNPadministration.

8. Absolute neutrophil count ≥ 1,500 cells/ul; hemoglobin ≥ 9 g/dl, platelets ≥ 100,000/ul

9. Serum creatinine ≤ 1.5 mg/dl, or calculated creatinine clearance ≥ 60 ml/min

10. Bilirubin ≤ upper limit of normal, alanine aminotransferase ≤ 1.5 x upper limit ofnormal and/or aspartate aminotransferase ≤ 1.5 x upper limit of normal, alkalinephosphatase ≤ 2.5 x upper limit of normal

11. Prothrombin time (PT)/international normalized ratio (INR) ≤ 1.5 x upper limit ofnormal

12. Activated partial thromboplastin (aPTT) time ≤ 1.5 x upper limit of normal

13. Female patients must have a negative urine or serum pregnancy at screening (pregnancy test is not required for patients with bilateral oophorectomy and/orhysterectomy or for those patients who are > 1 year postmenopausal)

14. All patients of reproductive potential must agree to use a medically acceptable formof contraception (eg, hormonal birth control, double-barrier method) or abstinence.

Exclusion Criteria:

1. Prior history or current diagnosis of leukemia

2. Have received any gene therapy products or oncolytic viral therapy

3. Receiving allopurinol

4. Received an investigational drug within 30 days prior to first injection of Ad/PNP

5. Received radiation treatment < 4 weeks prior to first injection of Ad/PNP, and doesnot have any RECIST 1.1 evaluable lesions that are outside the radiation field. (Ifthe patient has RECIST 1.1 evaluable lesions outside the radiation field then theycan be included.)

6. Received chemotherapy (systemic anticancer treatment) < 4 weeks prior to firstinjection of Ad/PNP and has not recovered from all the related side effects. (If thepatient has recovered from all related side effects or has reached a new baseline,then they may begin receiving treatment at sooner than 4 weeks)

7. Have significant baseline neuropathy (> Grade 2 based on Common Terminology Criteriafor Adverse events [CTCAE] v5.0)

8. Uncontrolled intercurrent disease (e.g., diabetes, hypertension, thyroid disease,active infection)

9. Had within 6 months prior to enrollment: Myocardial infarction, cerebral vascularaccident, uncontrolled congestive heart failure, significant liver disease, unstableangina

10. Fever (temperature > 38.1 degrees C orally)

11. Receiving chronic systemic corticosteroids (> 3 weeks) or any chronicimmunosuppressive medications within 14 days prior to first injection of Ad/PNP.Subjects receiving short courses of corticosteroids are considered eligible for thestudy.

12. Receiving anticoagulants other than those to maintain patency of venous lines

13. Women who are pregnant or breast feeding

14. History of HIV infection. No requirement for testing.