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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)
  1. Georgina V Long1,
  2. Reinhard Dummer2,
  3. Antoni Ribas3,
  4. Igor Puzanov4,
  5. Olivier Michielin5,
  6. Ari VanderWalde6,
  7. Robert HI Andtbacka7,
  8. Jonathan Cebon8,
  9. Eugenio Fernandez9,
  10. Josep Malvehy10,
  11. Anthony J Olszanski11,
  12. Thomas F Gajewski12,
  13. John M Kirkwood13,
  14. Olga Kuznetsova14,
  15. Lisa Chen15,
  16. David R Kaufman14,
  17. Jeffrey Chou15 and
  18. F Stephen Hodi16
  1. Aff1 grid.419690.30000000404916278Melanoma Institute Australia and The University of Sydney Sydney Australia
  2. Aff2 grid.412004.30000000404789977University Hospital of Zurich Zurich Switzerland
  3. Aff3 grid.413083.d0000000091428600University of California at Los Angeles Medical Center Los Angeles CA USA
  4. Aff4 grid.412807.80000000419369916Vanderbilt University Medical Center Nashville TN USA
  5. Aff5 grid.8515.90000000104234662Centre Hospitalier Universitaire Vaudois Lausanne Switzerland
  6. Aff6 grid.419930.6The West Clinic Memphis TN USA
  7. Aff7 grid.412722.00000000405153663University of Utah Huntsman Cancer Institute Salt Lake City UT USA
  8. Aff8 grid.414094.c0000000101627225Austin HealthAustin Hospital Heidelberg Australia
  9. Aff9 grid.150338.c0000000107219812Hôpitaux Universitaires de Genève Geneva Switzerland
  10. Aff10 grid.410458.c0000000096359413Hospital Clinic i Provincial de Barcelona Barcelona Spain
  11. Aff11 grid.412530.10000000404566466Fox Chase Cancer Center Philadelphia PA USA
  12. Aff12 grid.170205.10000000419367822The University of Chicago Medicine Chicago IL USA
  13. Aff13 grid.21925.3d0000000419369000University of Pittsburgh Cancer Institute Pittsburgh PA USA
  14. Aff14 grid.417993.10000000122600793Merck & Co., Inc. Kenilworth NJ USA
  15. Aff15 grid.417886.40000000106575612Amgen Inc. Thousand Oaks CA USA
  16. Aff16 grid.65499.370000000121069910Dana-Farber Cancer Institute Boston MA USA

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Meeting abstracts


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.


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