Phase II study of vincristine sulfate liposomes injection in patients with metastatic uveal melanoma

Abstract

9067 Background: Preclinical and clinical studies showed that liposomal encapsulation of vincristine sulfate (VCR) results in increased drug circulation time and accumulation of VCR at the tumor site. Marqibo has been administered safely at 2.25 mg/m2, a dose exceeding that typically employed for VCR ( dose capped at 2 mg), with tolerable clinical toxicities consistent with VCR. Of the 27 previously treated patients with metastatic melanoma in the Marqibo pharmacokinetic studies, 3 patients had a tumor response, including one patient with uveal melanoma metastatic to the lung that experienced a complete response. Methods: Patients with metastatic uveal melanoma with no more than one prior systemic therapy were enrolled. Patients with controlled brain metastases were allowed. Marqibo (2.25 mg/m2 by 1-hour intravenous infusion, no dose capping) was administered every 14 days until tumor progression. Responses were assessed every 6 weeks using the Response Evaluation Criteria in Solid Tumors (RECIST). Toxicity was assessed at least as frequently as before each dose. Results: Preliminary data is available for 22 enrolled patients (73% female). Median age was 65 years (range 38–79), 23% were previously treated with systemic chemotherapy, 86% had liver metastasis and 96% had M1c disease. Baseline serum LDH levels were elevated in 73% and were more than 2 × ULN in 37% of the patients. Twenty-one patients were evaluable for response; one patient discontinued the treatment after a single dose of therapy for toxicity without tumor progression. No patients died of drug toxicity while on the study. Twelve patients (57%) had stable disease. Estimated median survival is 6.4 months. Fourteen patients are alive, 2 for more than 12 months. Treatment related side effects were mostly grade 1 or 2; peripheral neuropathy was the only grade 3 toxicity, seen in 18% of the patients. The hematologic toxicities were minor; no neutropenia or thrombocytopenia was seen. Conclusions: Marqibo is well tolerated as single agent therapy in patients with advanced stage IV uveal melanoma. Its impact on the progression-free and overall survival of these critically ill patients will be presented. No significant financial relationships to disclose.