Phase II assessment of talabostat and cisplatin in second-line stage IV melanoma

This phase II, open label, single arm study was conducted to evaluate the safety and efficacy of 75–100 mg/m2 cisplatin combined with 300–400 mcg talabostat bid for 6, 21-day cycles. The primary endpoint was overall response. The rate of complete responses, duration of overall objective response, progression-free survival (PFS), and overall survival were the secondary endpoints.Six objective partial responses were recorded in the 74 patients (8.1%) in the intention-to-treat population. Five of these responses involved the 40 evaluable patients (12.5%). Thirty-one percent of patients reported SAEs to the combination of talabostat and cisplatin.Acceptable tolerability was observed in the intention-to-treat population and antitumor activity was observed in 12.5% of evaluable patients, which is not greater than historical expectation with cisplatin alone.Therapeutic options for advanced melanoma are limited to palliative management. No treatments have demonstrated survival advantage once metastatic lesions develop. Combination therapy produces the highest response rates, but overall survival remains less than 12 months. The combination chemotherapy of cisplatin/vinblastine/dacarbazine produces a response rate of 40% and a median overall survival of 9 months [1]. The regimen of cisplatin/dacarbazine/carmustine with or without tamoxifen results in a 15–52% response rate and median survival of 6.8–10.8 months [2-4]. The addition of the biochemotherapeutic agents, interferon-alpha (IFN-α) or interleukin-2 (IL-2), separately or in combination, produces a modest improvement in response rate, but without survival benefit [5-13] and with increased toxicity. Single-agent treatment has similarly failed to significantly improve survival; agents that have been used include dacarbazine [14], temozolomide [15], cisplatin [16], and nitrosoureas [15,17].Talabostat (valine-proline-boronic acid) together with other amino boronic dipeptides was originally designed as a high affinity, comp