Safety, tolerability and pharmacokinetic properties of the novel triazene TriN 2755 in tumour bearing dogs – a phase I study †

TriN 2755 is an alkylating antineoplastic agent for intravenous ( IV ) use, carrying the triazene group as the cytotoxic principal. Using a standard 3 + 3 design, a phase I study was performed in tumour bearing dogs to determine the maximum tolerated dose ( MTD ), the dose limiting toxicity ( DLT ), and pharmacokinetic ( PK ) profile of TriN 2755. Thirty dogs were included in the study. TriN 2755 was administered over 20 min on two consecutive weeks per month for a total of three cycles. The starting dose was 25 mg kg −1 and the MTD was 74.6 mg kg −1 . Three dogs experienced DLT , which was characterized by gastrointestinal adverse events. The PKs of TriN 2755 and its main metabolites in plasma and sputum are described in a two‐compartment model. The response rate for 19 of 30 dogs was 47.3% (six partial remission, three stable disease) and the median progression‐free interval ( PFI ) for the responders was 47 days (range: 21–450 days).