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  • Open Access

A Phase I/III, multicenter, open-label trial of talimogene laherparepvec (T-VEC) in combination with pembrolizumab for the treatment of unresected, stage IIIb-IV melanoma (MASTERKEY-265)

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Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P181

  • Published:


  • Melanoma
  • Herpes Simplex
  • Ipilimumab
  • Antitumor Immune Response
  • Plaque Form Unit


T-VEC is a herpes simplex virus-1-based oncolytic immunotherapy designed to selectively replicate in tumors, produce GM-CSF, and stimulate antitumor immune responses. OPTiM, a Phase III trial of T-VEC vs GM-CSF in unresectable stage IIIB-IV melanoma, improved the primary endpoint of durable response rate (DRR) in the T-VEC arm (16 vs 2%).[1] Pembrolizumab, a human programmed death receptor-1 (PD-1)-blocking antibody approved for the treatment of advanced metastatic or unresectable melanoma, has demonstrated superiority over the CTLA-4-blocking antibody ipilimumab in patients with stage III or IV melanoma that received no more than one prior line of systemic therapy (PFS HR 0.58, OS HR 0.63-0.69).[2] Combining T-VEC with pembrolizumab may enhance antitumor immune responses vs either therapy alone. Here, we describe a Phase Ib/III study assessing the safety and efficacy of T-VEC + pembrolizumab in unresected stage IIIB-IV melanoma. Twenty-one patients enrolled in Phase Ib December 2014 through March 2015 at 11 institutions in Australia, Spain, Switzerland, and the United States.


Primary objective for Phase Ib: assess dose-limiting toxicities of T-VEC + pembrolizumab. Key secondary objectives for Phase Ib: best OR, DRR, duration of response, disease control rate, PFS by investigator using modified immune-related response criteria (irRC), OS, treatment-emergent/related AEs, and potential blood/tumor biomarkers for response/resistance to combination treatment. Key eligibility criteria for Phase Ib: stage IIIB-IV melanoma naïve to systemic treatment (except adjuvant), injectable lesions, ECOG PS 0-1, no active cerebral metastases, no autoimmunity/immunosuppression, and no active herpetic infection. In Phase Ib, T-VEC is injected into cutaneous, subcutaneous, or nodal lesions at up to 4 mL of 106 plaque forming units (PFU)/mL day 1, then at up to 4 mL of 108 PFU/mL day 22 and Q2W. Pembrolizumab is given 200 mg IV Q2W. Treatment with both therapies continues until (whichever comes first): CR or PD per irRC, intolerance, for up to 2 yrs or, for T-VEC, when there are no longer injectable lesions. The randomized portion of the study comparing T-VEC + pembrolizumab to pembrolizumab alone was originally designed as a Phase II study. An updated Phase III design will be presented.

Trial registration identifier NCT02263508.

Authors’ Affiliations

Melanoma Institute Australia and The University of Sydney, Sydney, Australia
University Hospital of Zurich, Zurich, Switzerland
University of California at Los Angeles Medical Center, Los Angeles, CA, USA
Vanderbilt University Medical Center, Nashville, TN, USA
Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
The West Clinic, Memphis, TN, USA
University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA
Austin Health, Austin Hospital, Heidelberg, Australia
Hôpitaux Universitaires de Genève, Geneva, Switzerland
Hospital Clinic i Provincial de Barcelona, Barcelona, Spain
Fox Chase Cancer Center, Philadelphia, PA, USA
The University of Chicago Medicine, Chicago, IL, USA
University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
Merck & Co., Inc., Kenilworth, NJ, USA
Amgen Inc., Thousand Oaks, CA, USA
Dana-Farber Cancer Institute, Boston, MA, USA


  1. Andtbacka RH, Kaufman HL, Collichio F, et al: Talimogene Laherparepvec Improves Durable Response Rate in Patients with Advanced Melanoma. J Clin Oncol. 2015, doi:10.1200/JCO.2014.58.3377 [epub ahead of print]Google Scholar
  2. Robert C, Schachter J, Long GV, et al: Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015, 372: 2521-2532.PubMedView ArticleGoogle Scholar


© Long 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 (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.