Intratumoral Delivery of Viral Replicon (saRNA) Particles Expressing IL-12 in Head and Neck Cancer

Inclusion Criteria

• •1. Cohort A - Unresectable or recurrent/metastatic head and neck cancer with at least 1 injectable tumor not scheduled for tumor resection surgery. With one the following prior treatments:
• •Subjects must have received a platinum containing chemotherapy regimen, 5-Fluorouracil chemotherapy, taxane based chemotherapy, cetuximab or gemcitabine for treatment of primary tumor in locally advanced, or metastatic settings.
• •Subjects must have received an anti-PD-1/ PD-L1 as monotherapy or in combination with chemotherapy.
• •Subjects must have progressed following therapy with at least one PD-1 or PD-L1 checkpoint inhibitor (regardless of PD-L1 expression status).
• •Prior progression on a PD-1 or PD-L1 checkpoint inhibitor should be unequivocal; progression that occurs within the first 8 weeks of treatment on these agents should be confirmed with a second CT at least 4 weeks apart (to exclude pseudo-progression).
• •Patients with activating EGFR mutation or ALK rearrangement which is expected to be responsive to available tyrosine kinase inhibitor therapy, therefore these subjects must have been previously treated with an applicable tyrosine kinase inhibitor.
• •OR Cohort C - Patients with at least 1 measurable resectable lesion clinical stage I-IVb (cT1-4, N0-3) (AJCC, 8th Edition) (Amin, 2017), Histologically or cytologically confirmed HNSCC. Scheduled to undergo tumor surgical resection of the primary tumor.
• •2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1, and adequate bone marrow and organ function.
• •3. Primary tumors should be amenable to intratumoral (IT) injection \>1 cm diameter. This will be determined by the Protocol Director, or the surgeon involved.
• •4. Subjects with either a local recurrence or a new primary tumor will be allowed.
• •5. Age ≥ 18 years.
• •6. Have acceptable organ and marrow function defined as follows:
• •Absolute neutrophil count ≥ 1,500/mcL Platelets ≥ 100,000/mcL Hemoglobin ≥ 8.0 g/dL (Note: use of transfusion or other intervention to achieve Hgb ≥ 8.0 g/dL is acceptable) Total bilirubin ≤2x institutional upper limit of normal (ULN) AST(SGOT) or ALT(SGPT) ≤ 3.0x institutional ULN
• •7. Ability to understand and the willingness to provide written informed consent.
• •8. Life expectancy \> 12 weeks (about 3 months).
• •9. Patients must be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.