Advanced Melanoma
Conditions
Keywords
Advanced melanoma, Cutaneous melanoma
Brief summary
The purpose of this EAP is to provide expanded access (i.e., before marketing authorization) to vusolimogene oderparepvec (VO; herein referred to as VO) plus standard-of-care (SOC), nivolumab, for eligible patients diagnosed with advanced melanoma, who, in their treating physician's opinion, could benefit from this treatment.
Detailed description
The objective of treating with VO is to directly reduce or eliminate tumors by lytic virus replication and to induce a systemic anti-tumor immune response leading to tumor immunity and durable clinical responses. Limited treatment options are available to those patients with advanced melanoma who have progressed while on an anti-PD-1 therapy regimen, and the duration of progression-free survival (PFS) is less than 6 months with overall survival (OS) being less than 3 years. The mechanism of VO complements that of anti-PD-1 therapy such that combining VO with an anti-PD-1 agent, such as nivolumab, will increase the number of tumor-reactive T cells (through the action of VO) and relieve CD8-T cell exhaustion (through the action of the anti-PD-1 therapy). Combining VO with nivolumab, is supported by evidence in syngeneic immune-competent murine models demonstrating an increased reduction in tumor volume compared with either VO or anti-PD-1 monotherapy.
Interventions
BIOLOGICALRP1
Genetically modified Herpes Simplex Type 1 Virus
BIOLOGICALNivolumab
Anti-PD-1 Monoclonal Antibody
Sponsors
Replimune Inc.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Inclusion criteria
Patients must meet all of the following inclusion criteria to be eligible for inclusion in the program: 1. Voluntary agreement to provide written informed consent and a willingness and ability to comply with protocol requirements. 2. Male or female ≥18 years old. 3. Histologically, cytologically, or clinically confirmed diagnosis of unresectable or metastatic Stage IIIb though IV/M1a through M1d cutaneous melanoma, as per AJCC staging system, 8th edition. 4. Prior treatment with an anti-PD-1-containing regimen as monotherapy or in combination (i.e., LAG-3). 5. Has ≥ 1 measurable and injectable lesion of ≥ 1 cm in longest diameter (or shortest diameter for lymph nodes). 6. Has adequate hematologic function including: 1. White blood cell count ≥ 2.0 × 109/L 2. Absolute neutrophil count ≥ 1.5 × 109/L 3. Platelet count ≥ 75 × 109/L 4. Hemoglobin ≥ 8 g/dL (without packed red blood cell transfusion within 2 weeks of dosing) 7. Has adequate hepatic function, including: 1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN; \< 2.0 × ULN for patients with known Gilbert syndrome or liver metastases) 2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 × ULN (≤ 5.0 × ULN, if liver metastases are present) 3. Alkaline phosphatase (ALP) ≤ 2.5 × ULN (or ≤ 5.0 × ULN, if liver or bone metastases are present) 8. Has adequate renal function, defined as serum creatinine ≤ 1.5 × ULN or creatinine clearance ≤ 30.0 mL/minute/1.73 m2 (measured using Chronic Kidney Disease Epidemiology collaboration \[CKD-EPI\] formula) 9. Prothrombin time (PT) ≤ 1.5 × ULN (or international normalization ratio \[INR\] ≤ 1.3) and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN. Note: Patients which are on chronic anticoagulant therapy may be enrolled if the target international normalized ratio (INR) is ≤ 2.5. for patients requiring deep injection of VO, the INR must be \< 1.5 at the time of injection. 10. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 1. 11. Life expectancy of ≥ 3 months. 12. Male and female patients of reproductive potential must agree to avoid becoming pregnant or impregnating a partner and adhere to highly effective contraception requirement during treatment and for at 90 days after last dose of VO, or 5 months after last dose of nivolumab. 13. Women of childbearing potential must have a negative serum beta-human chorionic gonadotropin (β-hCG) test with a minimum sensitivity of 25 IU/L or equivalent units β-hCG within 7 days before the first dose of program treatment.
Exclusion criteria
Patients meeting any of the following
Outcome results
None listed