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

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 10 plaque forming units (PFU)/mL for the first dose, then 10 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.