RP1 for the Treatment of Melanoma Undergoing Sentinel Lymph Node Biopsy

Inclusion Criteria

• Be willing and able to provide written informed consent for the trial.
• Be ≥ 18 years of age on day of signing informed consent.
• Have a diagnosis of pT3b, T4a or T4b melanoma on biopsy. Patients must have grossly visible residual tumor, or a positive deep or lateral margin on initial biopsy. Patients with uveal melanoma are not eligible.
• Females of childbearing potential must have a negative beta-human chorionic gonadotropin (B-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units of B-hCG during screening, before the first dose, and a negative urine pregnancy test on days of treatment (day 1, 15 and 21).
• Female patients of reproductive potential must agree to avoid becoming pregnant and adhere to a highly effective contraception method until 90 days after last dose of RP1 alone. For a definition of highly effective contraceptive methods and instructions of patients and partners.
• Male patients of reproductive potential must agree to avoid impregnating a partner and adhere to a highly effective contraception method until 90 days after last dose of RP1 study agent and refrain from donating sperm during this period. For a definition of highly effective contraceptive methods and instructions of patients and partners. * Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Absolute neutrophil count (ANC) ≥ 1,000 /mcL (performed within 30 days of treatment initiation)
• Platelets ≥ 50,000 / mcL (performed within 30 days of treatment initiation)
• Hemoglobin ≥ 7 g/dL without transfusion or erythropoietin (EPO) dependency (within 7 days of assessment) (performed within 30 days of treatment initiation)
• Serum creatinine OR ≤ 1.5 X upper limit of normal (ULN) (performed within 30 days of treatment initiation)
• Measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) OR estimated (e)GFR 30 with the Creatine Phosphokinase Epidemiology Collaboration [CPK-Epi] calculation for subject with creatinine levels > 1.5 X institutional ULN (performed within 30 days of treatment initiation) * Creatinine clearance should be calculated per institutional standard.
• Serum total bilirubin ≤ 1.5 X ULN OR direct bilirubin ≤ ULN for subjects with total bilirubin levels > 1.5 ULN (performed within 30 days of treatment initiation)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) ≤ 2.5 X ULN (performed within 30 days of treatment initiation)
• Prothrombin time (PT) or international normalization ratio (INR) ≤ 1.5 x ULN, and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN (performed within 30 days of treatment initiation) * Note: Patients who are on chronic anticoagulant therapy may be enrolled if pretreatment INR < 2.5 x ULN

Exclusion Criteria

• Prior treatment with an oncolytic virus therapy.
• Has acute or chronic active hepatitis B and C virus infection or known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive) or known active hepatitis C virus (HCV) (defined as HCV ribonucleic acid [RNA] [qualitative]) or HIV infection. * Note: No testing for Hepatitis B, Hepatitis C, or HIV is required unless mandated by local health authority or clinically indicated.
• Had systemic infection requiring intravenously (IV) antibiotics or other serious infection within 14 days prior to dosing.
• Have active significant herpetic infections or prior complications of herpes simplex virus (HSV)-1 infection (e.g., herpetic keratitis or encephalitis).
• Conditions requiring treatment with immunosuppressive doses (> 10 mg daily prednisone or equivalent) of systemic corticosteroids other than for corticosteroid replacement therapy within 14 days after enrollment.
• Major surgery ≤ 1 week prior to starting study drug. * Note: Patients who undergo major surgery must adequately recover prior to starting study treatment.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within four weeks prior to the first dose of study treatment.
• History of documented allergic reactions or acute hypersensitivity reactions attributed to RP1 or any of its excipients.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed, however, intranasal influenza vaccines (e.g., FluMist [trademark]) are live attenuated vaccines and are not allowed. * Note: Available COVID-19 vaccines do not contain live virus.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that will be unfavorable for the administration of study drug or affect the explanation of drug toxicity or adverse events (AEs) or interfere with the patient’s participation for the full duration of the study or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
• Has serious or uncontrolled medical disorders.
• Has known psychiatric, alcohol abuse, or substance abuse disorders that would interfere with cooperating with the requirements of the study.
• Is a person deprived of their liberty by a judicial or administrative decision, or an adult person subject to a legal protection measure.
• Is a solid organ transplant recipient.
• Has a concurrent malignancy requiring active systemic therapy or ongoing radiation.
• Patients with tumors that are located near critical structures, such as the carotid artery or portal vein, or scalp lesions presenting with moderate to extensive bone erosion and tumors that may have invaded the heart, great vessels, or other critical structures will not be eligible because these area should not be injected. Injection through an ulcerated area of a lesion should be avoided.