Phase 1b Trial of Biweekly Intravenous Pexa-Vec (JX-594), an Oncolytic and Immunotherapeutic Vaccinia Virus in Colorectal Cancer

• Published in: Molecular therapy Vol. 23; no. 9; pp. 1532 - 1540
• Main Authors: Park, Se Hoon, Breitbach, Caroline J, Lee, Jeeyun, Park, Joon Oh, Lim, Ho Yeong, Kang, Won Ki, Moon, Anne, Mun, Jae-Hee, Sommermann, Erica M, Maruri Avidal, Liliana, Patt, Rick, Pelusio, Adina, Burke, James, Hwang, Tae-Ho, Kirn, David, Park, Young Suk
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2015; Elsevier Limited; Nature Publishing Group
• Subjects: Administration, Intravenous; Adult; Aged; Antibodies; Cancer therapies; Chemotherapy; Colorectal cancer; Colorectal Neoplasms - genetics; Colorectal Neoplasms - immunology; Colorectal Neoplasms - mortality; Colorectal Neoplasms - pathology; Colorectal Neoplasms - therapy; Combined Modality Therapy; Cytokines - blood; Drug Administration Schedule; Drug dosages; Female; Genetic Vectors - administration & dosage; Genetic Vectors - genetics; Granulocyte-Macrophage Colony-Stimulating Factor - genetics; Hematology; Humans; Immunotherapy - adverse effects; Immunotherapy - methods; Kinases; Leukocyte Count; Liver; Lymphatic system; Male; Metastasis; Middle Aged; Neoplasm Metastasis; Oncology; Oncolytic Virotherapy - adverse effects; Oncolytic Virotherapy - methods; Oncolytic Viruses - genetics; Original; Patients; Pharmacokinetics; Skin Diseases - etiology; Skin Diseases - pathology; Toxicology; Treatment Outcome; Tumors; Vaccinia virus; Vaccinia virus - genetics; Viruses; New York; United States > US; California
• ISSN: 1525-0016; 1525-0024
• DOI: 10.1038/mt.2015.109

Fifteen patients with treatment-refractory colorectal cancer were enrolled on a phase 1b study of Pexa-Vec (pexastimogene devacirepvec; JX-594), an oncolytic and immunotherapeutic vaccinia designed to selectively replicate in cancer cells. Pexa-Vec was administered intravenously every 14 days, at dose levels of 1 × 106, 1 × 107, or 3 × 107 plaque-forming units (pfu)/kg. The primary endpoint was to determine the maximum tolerated dose. Secondary endpoints were pharmacokinetics and pharmacodynamics as well as antitumor activity. Patients were heavily pretreated (mean 4.5 lines of therapy). All patients received at least two Pexa-Vec doses (median = 4; range = 2–4). No dose-limiting toxicities were reported, and the maximum tolerated dose was not reached. The most common adverse events were grade 1/2 flu-like symptoms, generally lasting <24 hours. During the first and last cycles, genome pharmacokinetics were unchanged. Infectious pfu could be detected in plasma up to 2 hours after cycle 1 and up to 30 minutes after cycle 4 (when antivaccinia antibody titers are known to have peaked). Ten patients (67%) had radiographically stable disease. Given the acceptable safety profile of multiple intravenous Pexa-Vec infusions in patients with treatment-refractory colorectal cancer, further trials evaluating efficacy of intravenous Pexa-Vec, as monotherapy or in combination with chemotherapeutic agents, is warranted in this patient population.