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A Phase I, multicenter, open-label trial to evaluate the safety of talimogene laherparepvec (T-VEC) injected into liver tumors

  • 1,
  • 1,
  • 2,
  • 3,
  • 4,
  • 5,
  • 5 and
  • 6
Journal for ImmunoTherapy of Cancer20153(Suppl 2):P180

https://doi.org/10.1186/2051-1426-3-S2-P180

Published: 4 November 2015

Keywords

  • Liver Tumor
  • Maximum Tolerate Dose
  • Compute Tomography Guidance
  • Dose Cohort
  • Metastatic Liver Tumor

Introduction

T-VEC, an intralesionally-delivered oncolytic immunotherapy, is a herpes simplex virus-1 engineered to selectively replicate in tumors and stimulate an anti-tumor immune response through expression of GM-CSF. T-VEC has the ability to lyse various cancer cell types in vitro[1]. A Phase III study of T-VEC injected into skin, subcutaneous, or lymph node tumors versus subcutaneous GM-CSF in advanced melanoma demonstrated improved durable response rate for T-VEC, with regression of both injected and uninjected lesions[2]. To further explore if different types of cancers and locations might be treatable with T-VEC, this Phase I study evaluates whether primary and metastatic liver tumors may be safely and effectively injected with T-VEC.

Methods

Approximately 100 patients will be enrolled. Primary objective: evaluate maximum tolerated dose (MTD) of intrahepatic injection of T-VEC by patient incidence of dose-limiting toxicities (DLTs). Key secondary objectives: overall safety, efficacy, and biodistribution of T-VEC. Key eligibility criteria: breast, colorectal, gastroesophageal, kidney, lung cancer or melanoma with liver metastases (non-HCC) or hepatocellular carcinoma (HCC); measurable liver tumors suitable for injection; ECOG performance status 0-1; life expectancy ≥5 months; ≥1 prior standard systemic anticancer therapy (non-HCC); Child-Pugh A-B7; no detectable hepatitis B/C viral load; not a candidate for surgery or locoregional therapy of liver tumors with curative intent or planned systemic anticancer therapy; tumor in < 1/3 of the liver; no macroscopic intravascular invasion. The study consists of two parts. Part 1: 3+3 dose escalation of 3 sequential dose cohorts each administering T-VEC in increasing concentrations (107 or 108 PFU/mL) and volumes (up to 4 or 8 mL). MTD for HCC is determined separately from non-HCC tumor types; HCC cohorts will not proceed until safety at respective dose levels are determined in non-HCC. Six T-VEC doses injected under ultrasound or computed tomography guidance q21 (±3) days are planned, with an investigator option to continue for up to 6 additional doses. The first dose of T-VEC in all dose cohorts is given at 106 PFU/mL. Part 2: 7 expansion cohorts for each cancer type with 10 patients each administered the MTD of T-VEC determined from Part 1.

Authors’ Affiliations

(1)
David Geffen School of Medicine at UCLA, Los Angeles, USA
(2)
Stanford University School of Medicine, Stanford, USA
(3)
Washington University School of Medicine, St. Louis, USA
(4)
Rutgers Cancer Institute of New Jersey, New Brunswick, USA
(5)
Amgen Inc., Thousand Oaks, USA
(6)
Moores Cancer Center, University of California, San Diego, La Jolla, USA

References

  1. Liu BL, Robinson M, Han ZQ, et al: ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties. Gene Ther. 2003, 10 (4): 292-303.PubMedView ArticleGoogle Scholar
  2. Andtbacka RH, Kaufman HL, Collichio F, et al: Talimogene Laherparepvec Improves Durable Response Rate in Patients with Advanced Melanoma. J Clin Oncol. 2015, PubMed PMID: 26014293 [Epub ahead of print]Google Scholar

Copyright

© Hecht et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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