Phase 2 Study Of Talabostat And Cisplatin In Stage Iv Melanoma.

7563 Background: Talabostat (T) is an oral inhibitor of dipeptidyl peptidases including fibroblast activation protein found on the stroma of tumors and in melanomas. T stimulates cytokine and chemokine production resulting in specific T-cell immunity and T-cell-independent activity. T significantly enhances cisplatin (C) activity in mice, and reduced tumor size >60% in melanoma xenografts (A375, A2058) in immunodeficient mice. Therefore, a clinical trial of this combination in patients with metastatic melanoma was warranted. Methods: An open-label, single-arm, Phase 2 study is underway in up to 54 evaluable patients with Stage IV melanoma. Six 3-week cycles of C-100mg/m2 (Day1) and T-300μg administered orally BID on Days 2–15. Dose-escalation of T to 400μg BID is allowed in subsequent cycles depending on tolerability. Single-agent T can then be continued beyond 6 cycles at the discretion of the investigator. Eligible patients have received no more than 1 prior bio- or chemotherapy regimen, have an ECOG PS 0–2 with measureable disease per RECIST, no symptomatic CNS metastases, LDH, ALT, and AST <3X ULN. The primary endpoint is disease response with secondary endpoints including survival, duration of response, time-to-progression, and incidence of clinically-significant events of neutropenia or anemia. Results: 23 patients have been enrolled to date, 15 men and 8 women with a median age of 55 (range 27–78). Sixteen patients had 1 prior treatment and 7 are treatment-naive for Stage IV disease. Thirteen patients are continuing on study with four out to at least 12 weeks of treatment. Three patients have evidence of clinical activity with significant decreases in measureable skin lesions (2 patients) or thoracic adenopathy (1 patient). The most frequently reported adverse events are nausea (56%), fatigue (35%), and vomiting (26%). Edema/peripheral swelling and anxiety are reported in 17%. Grade 3/4 events included nausea/vomiting in 3 patients, pain, dizziness, and pneumonia (in one patient each). Conclusions: The combination of T and C shows activity in metastatic melanoma and can be safely administered. Nausea, fatigue, and vomiting are the most common AEs. Enrollment is continuing and updated study results will be presented at the annual meeting. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Point Therapeutics Point Therapeutics Point Therapeutics Point Therapeutics