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
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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
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.
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.
Advancement into the randomized phase 2 is planned pending Data Review Team recommendations.
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Society for Immunotherapy of Cancer 28th Annual Meeting