A Phase 1b/2 Study of PV-10 Intralesional Injection in Combination With Systemic Immune Checkpoint Inhibition for Treatment of Metastatic Melanoma
This is an international multicenter, open-label, sequential phase study of intralesional (IL) PV-10 in combination with immune checkpoint inhibition. Metastatic melanoma patients (Stage IV or Stage III unresectable, in-transit or satellite disease) with at least one injectable lesion who are candidates for pembrolizumab (both treatment naïve patients and treatment refractory patients who have failed to achieve a complete or partial response to or previously progressed on one or more checkpoint inhibitor) will be eligible for study participation. In the Phase 1b portion of the study, all participants will receive the combination of IL PV-10 and pembrolizumab (i.e., PV-10 + standard of care). In the subsequent Phase 2 portion of the study participants will be randomized 1:1 to receive either the combination of IL PV-10 and pembrolizumab or pembrolizumab alone (i.e., PV-10 + standard of care vs. standard of care).
• Age 18 years or older, male or female.
• Histologically or cytologically confirmed diagnosis of melanoma.
• Stage IV or Stage III (unresectable, in-transit or satellite) melanoma.
• At least 1 Injectable Lesion (i.e., cutaneous, subcutaneous, soft tissue, superficial nodal or palpable nodal lesion with longest diameter at least 5 mm that is suitable for injection with PV-10).
• A minimum of 1 measurable Target Lesion that can be accurately measured by calipers, computed tomography (CT) or magnetic resonance imaging (MRI) consisting of at least one of the following:
‣ at least one cutaneous lesion (each lesion ≥ 10 mm longest diameteror up to 5 lesions in aggregate having a sum of longest diameters ≥ 10 mm); and/or
⁃ at least one subcutaneous or soft tissue lesion (each lesion ≥ 10 mm in longest diameter by CT or MRI); and/or
⁃ at least one nodal lesion (each lesion ≥ 15 mm in short axis diameter by CT or MRI); and/or
⁃ at least one visceral lesion (each lesion ≥ 10 mm in longest diameter by CT or MRI).
• Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-1.
• Clinical Laboratories:
‣ absolute neutrophil count (ANC) ≥ 1.5 x 109/L and platelet count ≥100 x 109/L
⁃ estimated creatinine clearance (CrCl, by Cockcroft-Gault formula) or estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2
⁃ total bilirubin ≤ 3 times the upper limit of normal (ULN)
⁃ aspartate transaminase (AST), alanine transaminase (ALT) and alkaline phosphatase (ALP) ≤ 5 times the upper limit of normal (ULN)
• Thyroid function abnormality ≤ Common Toxicity Criteria for Adverse Effects (CTCAE) Grade 2.