High-dose Allovectin-7 in patients with advanced metastatic melanoma: final phase 2 data and design of phase 3 registration trial.
7543 Background: Allovectin-7, a bicistronic plasmid formulated with a cationic lipid system and encoding HLA-B7 and β-2 microglobulin, is an immunotherapeutic designed to induce a pro-inflammatory response and express allogenic MHC-class I antigen upon intralesional administration. METHODS: We have conducted a Phase 2 dose-escalation trial to evaluate the safety and efficacy of Allovectin-7 in patients with metastatic melanoma. Eligible patients had stage III or IV metastatic melanoma recurrent or unresponsive to prior therapy; injectable lesion(s); ECOG PS 0-1 and adequate organ function. Patients with brain or visceral (except lung) metastases, abnormal LDH, or any lesion ≥100 cm(2) were excluded. Patients with 2 or more injectable lesions were randomized to receive injections of 2 mg Allovectin-7 divided for injection for up to 5 lesions. Patients received weekly intratumoral injections of a total of 2 mg of Allovectin-7 for 6 weeks followed by 3 weeks of observation and evaluation. Overall Response (OR) was assessed using RECIST guidelines two weeks following the last injection of each cycle. Patients with stable or responding disease received additional cycles of Allovectin-7. RESULTS: Final, audited data are presented for the 133 patients enrolled. All patients were evaluated for safety (6 patients in the dose-escalation stage and 127 patients in the 2 mg efficacy stage), and 127 patients were evaluated for efficacy. Fifteen patients (11.8%, 95% CI: 6.2-17.4) achieved an objective response lasting a median duration of 12.7 months (95% CI: 8.3 - ongoing). The responders include two patients who had lesions resected and found no evidence of melanoma. Median time to progression was 1.6 months and median overall survival was 21.3 months (95% CI: 14.8-33.4). There were no reported Grade 3 or Grade 4 adverse events associated with Allovectin-7. CONCLUSIONS: Results indicate that high-dose Allovectin-7 is an active, well-tolerated treatment for Stage III/IV metastatic melanoma patients with injectable cutaneous, subcutaneous, or nodal lesions. The details of the Phase 3, follow-up clinical trial design will be presented. [Table: see text].
Richards, JM; Bedikian, A; Gonzalez, R; Atkins, MB; Whitman, E; Lutzky, J; Morse, MA; Amatruda, T; Galanis, E; Thompson, J; Vical Clinical Research Operations Team,
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