8578 Background: Significant toxicity limits the systemic delivery of high-dose recombinant Interleukin-2 (IL-2). An alternative method for extended dosing of IL-2 that may reduce toxicity is by intratumoral injection of IL-2 plasmid DNA (pDNA) with electroporation (EP). Methods: A phase I dose-escalation trial is ongoing in subjects with metastatic melanoma to evaluate the safety of intratumoral delivery of IL-2 pDNA (VCL-IM01, Vical Inc., San Diego, CA) followed by EP (MedPulser DNA EPT System, Inovio, San Diego, CA). Eligible subjects have recurrent metastatic melanoma; an injectable lesion = 1 cm2 and < 25 cm2; ECOG 0 or 1; LDH = 1.5 × ULN, and no brain or liver metastases. In the dose-escalation stage of the trial, 3 subjects in each dose cohort received up to 2 cycles of treatment, each consisting of 4 weekly injections followed by a 4-week observation period. Dose levels included 0.5, 1.5, 5.0 mg/tumor, and 15.0 mg (5 mg in each of 3 tumors). A safety assessment was conducted for each cohort prior to enrollment of the next cohort. In the 2nd trial stage, 17 subjects are to be enrolled at the maximum tolerated dose (MTD). The observation period is shortened to 2 weeks between cycles. For all subjects, safety is assessed at every visit. Results: 12 subjects (7 male, 5 female) were enrolled in the dose escalation stage, 3 subjects at each dose. Ages range from 38 to 86 years. No Grade 3 or 4 adverse events (AEs) were reported related to study drug or procedures. All related AEs (12 reported) were Grade 1: 5 related to study drug, 4 to the EP procedure, and 3 to both. Injection site pain was the most common AE. No dose-limiting toxicities occurred; thus the MTD was defined as the 15 mg dose (5 mg/tumor in 3 tumors). To date, 6/17 subjects in Stage 2 of the trial (5 mg/tumor, up to 3 tumors injected) have been enrolled with no Grade 3 or 4 AEs related to study drug or injection/EP procedures. Physicians have observed responses in treated and untreated lesions. Overall response data will be presented. Conclusions: Intratumoral administration of IL-2 pDNA with EP appears safe and well tolerated in 18 patients with metastatic melanoma when given up to a 15 mg dose (5 mg/tumor). Preliminary indications of decreased tumor size suggest local and systemic activity of IL-2 pDNA with EP. No significant financial relationships to disclose.
Phase I trial of biochemotherapy with cisplatin, temozolomide, and dose escalation of nab-paclitaxel combined with interleukin-2 and interferon-α in patients with metastatic melanoma