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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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          Abstract

          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

          Conference
          J Immunother Cancer
          J Immunother Cancer
          Journal for Immunotherapy of Cancer
          BioMed Central
          2051-1426
          2013
          7 November 2013
          : 1
          : Suppl 1
          : P84
          Affiliations
          [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
          Article
          2051-1426-1-S1-P84
          10.1186/2051-1426-1-S1-P84
          3991001
          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 ( http://creativecommons.org/licenses/by/2.0), 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
          Categories
          Poster Presentation

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