title: Phase 1b Trial of Biweekly Intravenous Pexa-Vec (JX-594), an Oncolytic and Immunotherapeutic Vaccinia Virus in Colorectal Cancer.
abstract: 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 × 10(6), 1 × 10(7), or 3 × 10(7) 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.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University Samsung Medical Center, Seoul, Korea.
authors.forename: Se Hoon
authors.initials: SH
authors.lastname: Park
authors.affiliation: SillaJen Biotherapeutics, Inc., San Francisco, California, USA.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Breitbach
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University Samsung Medical Center, Seoul, Korea.
authors.forename: Jeeyun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University Samsung Medical Center, Seoul, Korea.
authors.forename: Joon Oh
authors.initials: JO
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University Samsung Medical Center, Seoul, Korea.
authors.forename: Ho Yeong
authors.initials: HY
authors.lastname: Lim
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University Samsung Medical Center, Seoul, Korea.
authors.forename: Won Ki
authors.initials: WK
authors.lastname: Kang
authors.affiliation: SillaJen Biotherapeutics, Inc., San Francisco, California, USA.|Current address: Aduro Biotech, Berkeley, California.
authors.forename: Anne
authors.initials: A
authors.lastname: Moon
authors.affiliation: SillaJen, Inc., Busan, Korea.
authors.forename: Jae-Hee
authors.initials: JH
authors.lastname: Mun
authors.affiliation: SillaJen, Inc., Busan, Korea.
authors.forename: Erica M
authors.initials: EM
authors.lastname: Sommermann
authors.affiliation: SillaJen, Inc., Busan, Korea.
authors.forename: Liliana
authors.initials: L
authors.lastname: Maruri Avidal
authors.affiliation: RadMD, New York, New York, USA.
authors.forename: Rick
authors.initials: R
authors.lastname: Patt
authors.affiliation: SillaJen Biotherapeutics, Inc., San Francisco, California, USA.
authors.forename: Adina
authors.initials: A
authors.lastname: Pelusio
authors.affiliation: SillaJen Biotherapeutics, Inc., San Francisco, California, USA.
authors.forename: James
authors.initials: J
authors.lastname: Burke
authors.affiliation: SillaJen, Inc., Busan, Korea.|Department of Pharmacology, School of Medicine, Pusan National University, Busan, Korea.
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Hwang
authors.affiliation: SillaJen Biotherapeutics, Inc., San Francisco, California, USA.
authors.forename: David
authors.initials: D
authors.lastname: Kirn
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University Samsung Medical Center, Seoul, Korea.
authors.forename: Young Suk
authors.initials: YS
authors.lastname: Park
mesh_terms: D061605:Administration, Intravenous; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D004334:Drug Administration Schedule; D005260:Female; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics*; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D050130:Oncolytic Virotherapy / Q000009:adverse effects / Q000379:methods; D050504:Oncolytic Viruses / Q000235:genetics*; D012871:Skin Diseases / Q000209:etiology / Q000473:pathology; D016896:Treatment Outcome; D014616:Vaccinia virus / Q000235:genetics*
chemical_list: D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor