Abstract
Talimogene laherparepvec (T-VEC) is approved for the treatment of unresectable melanoma in the USA, Europe, and Australia. This phase I, multicenter, open-label, dose de-escalation study evaluated the safety and efficacy of T-VEC in Japanese patients with unresectable stage IIIB-IV melanoma. Eligible adult patients had histologically confirmed stage IIIB-IVM1c cutaneous melanoma, may have received prior systemic anticancer therapy, must have had ≥1 injectable lesion, serum lactate dehydrogenase ≤1.5x upper limit of normal, ECOG performance status of 0 or 1, and adequate hematologic, hepatic, and renal function. T-VEC was injected intralesionally (first dose, ≤4.0 ml of 10(6) PFU/ml; after 3 weeks and then every 2 weeks thereafter, ≤4.0 ml of 10(8) PFU/ml). Primary endpoints were dose-limiting toxicities (DLTs) and durable response rate (DRR). Of 18 enrolled patients (72.2% female), 16 had received ≥1 prior line of therapy. Ten patients discontinued T-VEC due to disease progression. Median (range) follow-up was 20.0 (4-37) months. No DLTs were observed; 17 (94.4%) patients had treatment-emergent adverse events (AEs). Fourteen (77.8%) patients had treatment-related AEs; the most frequent were pyrexia (44.4%), malaise (16.7%), chills, decreased appetite, pruritus, and skin ulcer (11.1% each). The primary efficacy endpoint was met: 2 (11.1%) patients had a durable partial response ≥6 months. The DRR was consistent with that observed in a phase III trial of T-VEC in non-Asian patients. The safety profile was consistent with the patients' underlying disease and the known safety profile of T-VEC.