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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. Igor Puzanov1,
  2. Mohammed Milhem2,
  3. Robert Andtbacka3,
  4. David Minor4,
  5. Omid Hamid5,
  6. Ai Li6,
  7. Ari VanderWalde6 and
  8. Howard Kaufman7
  1. Aff1 grid.152326.10000000122647217Vanderbilt University Nashville TN USA
  2. Aff2 grid.214572.70000000419368294University of Iowa Iowa City IA USA
  3. Aff3 grid.412722.00000000405153663Huntsman Cancer Institute Salt Lake City UT USA
  4. Aff4 grid.17866.3e0000000098234542California Pacific Center San Francisco CA USA
  5. Aff5 grid.488730.0The Angeles Clinic and Research Institute Los Angeles CA USA
  6. Aff6 grid.417886.40000000106575612Amgen Inc. Thousand Oaks CA USA
  7. Aff7 grid.262743.60000000107058297Rush University Chicago IL USA

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Meeting abstracts

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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