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A phase 2 study of high-dose Allovectin-7 in patients with advanced metastatic melanoma

Bedikian, Agop Y.a; Richards, Jonb; Kharkevitch, Dmitric; Atkins, Michael B.d; Whitman, Erice; Gonzalez, Renef

doi: 10.1097/CMR.0b013e3283390711
ORIGINAL ARTICLES: Clinical research

Allovectin-7, a bicistronic plasmid encoding human leukocyte antigen-B7 and β-2 microglobulin formulated with a cationic lipid system, is an immunotherapeutic agent designed to express allogeneic major histocompatibility complex class I antigen upon intralesional administration. A phase 2 dose-escalation study (VCL-1005-208) was conducted 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, an Eastern Cooperative Oncology Group performance status 0 or 1, and adequate organ function. Patients with brain or visceral (except lung) metastases, abnormal lactate dehydrogenase, or any lesion greater than 100 cm2 were excluded. Patients received six weekly intralesional injections followed by 3 weeks of observation and evaluation. Overall response was assessed using Response Evaluation Criteria in Solid Tumors guidelines. Patients with stable or responding disease were eligible to receive additional cycles of Allovectin-7. All 133 patients were evaluated for safety and 127 patients (2 mg, high dose) were evaluated for efficacy. Fifteen patients (11.8%, 95% confidence interval: 6.2–17.4) achieved an objective response with median duration of response of 13.8 months (95% confidence interval: 8.5, not estimable). A histological examination of tissue from two responding patients who had their lesions resected has shown no evidence of melanoma. Median time-to-progression in this study was 1.6 months. In conclusion, these results indicate that high-dose Allovectin-7 seems to be an active, well-tolerated treatment for selected stage III/IV metastatic melanoma patients with injectable cutaneous, subcutaneous, or nodal lesions.

aDepartment of Melanoma Medical Oncology, MD Anderson Cancer Center, Houston, Texas

bOncology Specialists Research Institute, Park Ridge, Illinois

cDepartment of Clinical Development, Vical Incorporated, San Diego, California

dDepartment of Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts

eOffice of Grants and Research, Atlantic Melanoma Center, Morristown, New Jersey

fDepartment of Cutaneous Oncology, University of Colorado Health Sciences Center, Aurora, Colorado, USA

Correspondence to Dmitri Kharkevitch, MD, PhD, Vical Incorporated, 10390 Pacific Center Court, San Diego, CA 92121, USA

Tel: +1 858 646 1230; fax: +1 858 334 1467;

e-mail: dkharkevitch@vical.com

Received 11 May 2009 Accepted 27 January 2010

© 2010 Lippincott Williams & Wilkins, Inc.