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      Phase 1 results of a phase 1b/2, multicenter, open-label trial to evaluate safety and efficacy of talimogene laherparepvec (T-VEC) and ipilimumab (ipi) vs ipi alone in previously untreated, unresected stage IIIB-IV melanoma

      , 1 , 2 , 3 , 4 , 5 , 6 , 6 , 7

      Journal for Immunotherapy of Cancer

      BioMed Central

      Society for Immunotherapy of Cancer 28th Annual Meeting

      8-10 November 2013

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          Introduction T-VEC is a herpes simplex virus type-1-derived oncolytic immunotherapy designed to produce GM-CSF and to selectively replicate in and lyse tumors to induce a systemic anti-tumor immune response. A phase 3 study of T-VEC in Stage IIIB-IV melanoma demonstrated a significant improvement in ≥ 6 mo durable response rate vs GM-CSF and a tolerable safety profile. Methods In this 2-part study (NCT01740297), phase 1b evaluated the safety of T-VEC in combination with ipi as assessed by the incidence of dose-limiting toxicities (DLTs) at full doses of both agents. For 6 to 9 patients (pts) evaluable for DLT, approximately 18 pts were to be enrolled in phase 1b. DLTs were defined as any grade (gr) ≥ 3 immune-related adverse event (AE) or gr ≥ 4 AE of any etiology occurring between the first dose of ipi and 6 wks after. The incidence of DLTs was required to be ≤ 1 of the first 6 evaluable pts or ≤ 2 of the first 9 evaluable pts (if 2 DLTs were seen in the first 6 pts). Key entry criteria were previously untreated, unresectable Stage IIIB-IV melanoma, ECOG 0-1, measurable disease, and ≥ 1 injectable cutaneous, subcutaneous, or nodal tumor. T-VEC was administered by intralesional injection at ≤ 4 mL of 106 plaque forming units (PFU)/mL for the first dose, then 108 PFU/mL on day 1 of wk 4 and thereafter. Ipi 3 mg/kg q3w was administered as 4 infusions starting at wk 6. Pts received T-VEC until development of DLT, all injectable tumors have disappeared, disease progression per the Immune Related Response Criteria, or treatment intolerance. Phase 2 will evaluate the safety and efficacy of ipi vs T-VEC+ipi in a randomized fashion. Results To date, 19 pts have enrolled (13 pts received ≥ 1 dose of T-VEC); 9 pts are evaluable for DLT. All DLT evaluable pts received at least 4 doses of T-VEC and 2 doses of ipi by the time of DLT cutoff (6 wks post first ipi dose). No DLTs were observed in evaluable pts. Serious AEs were reported in 1 of 19 pts to date (gr 3 nausea and abdominal distention in week 11 of treatment). Two partial responses were reported by wk 12 in the 9 DLT evaluable pts. Data will be updated at the meeting. Conclusions Advancement into the randomized phase 2 is planned pending Data Review Team recommendations.

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          Author and article information

          J Immunother Cancer
          J Immunother Cancer
          Journal for Immunotherapy of Cancer
          BioMed Central
          7 November 2013
          : 1
          : Suppl 1
          : P84
          [1 ]Vanderbilt University, Nashville, TN, USA
          [2 ]University of Iowa, Iowa City, IA, USA
          [3 ]Huntsman Cancer Institute, Salt Lake City, UT, USA
          [4 ]California Pacific Center, San Francisco, CA, USA
          [5 ]The Angeles Clinic and Research Institute, Los Angeles, CA, USA
          [6 ]Amgen Inc., Thousand Oaks, CA, USA
          [7 ]Rush University, Chicago, IL, USA
          Copyright © 2013 Puzanov et al; licensee 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.

          Society for Immunotherapy of Cancer 28th Annual Meeting
          National Harbor, MD, USA
          8-10 November 2013
          Poster Presentation


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