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Volume 3 Supplement 2

30th Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2015)

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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)


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.


  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]

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  2. Robert C, Schachter J, Long GV, et al: Pembrolizumab versus Ipilimumab in Advanced Melanoma. N Engl J Med. 2015, 372: 2521-2532.

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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.

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Long, G.V., Dummer, R., Ribas, A. et al. 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). j. immunotherapy cancer 3 (Suppl 2), P181 (2015).

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