Dose Ranging, Toxicity Seeking, Phase 1 Trial of Oncolytic Adenoviral Therapy for Melanoma Intracranial and Extracranial Metastases

Inclusion criteria

• ✓.Patients must be able to complete an MRI of the head with contrast. 5.For women of childbearing potential only, a negative urine or serum pregnancy test is required at screening. Women must agree to notify investigator immediately if they become pregnant at any time during the trial period.
• ✓.Men and women of childbearing potential must be willing to employ adequate contraception throughout the study and for men for up to 6 months from administration of virus. Birth control that is acceptable to use in this study:
• ✓.Patients must be able and willing to provide informed consent. A legally authorized representative (LAR) may provide consent if the potential subject lacks the capacity to provide consent themselves. Patient assent will be sought where feasible in this situation.
• ✓.- For patients enrolled in Groups A and B, patients must be relapsed or refractory to standard of care therapy. Additionally, patients must continue with immunotherapy while undergoing oncolytic viral treatment at the discretion of the medical oncologist. 9. Patients enrolled in Group A or Group B must be on one of the following FDA approved immunotherapy agents: Ipilimumab, Nivolumab, Pembrolizumab, Relatlimab.
• ✓. Patients must have radiographic evidence of stable extracranial disease or no evidence of extracranial disease on current immunotherapy regimen based on RECIST v1.1 criteria.
• ✓. Patients must have between one and five brain metastases secondary to intracranial disease progression, identified on the screening MRI, from histologically confirmed metastatic melanoma. At least one of those lesions must be untreated, be suitable for accurate repeated measurements and have a tumor diameter of either 1.0-3.5cm (Group A- Arm 1) or 1.0-2.0cm (Group A- Arm 2) on the screening magnetic resonance imaging \[MRI\]) in at least one dimension. One of those lesions will be designated as the index lesion and planned for stereotactic intraoperative biopsy to ensure viable tumor tissue and oncolytic viral administration. The other four may be newly diagnosed, stable or recurrent.