Phase I dose-escalation study evaluating safety, tolerability and pharmacokinetics of MEDI-573, a dual IGF-I/II neutralizing antibody, in Japanese patients with advanced solid tumours
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Purpose This Phase I, open-label, single-arm, dose-escalation study aimed to evaluate the safety and tolerability of the insulin-like growth factor (IGF-I/II) neutralizing antibody, MEDI-573, in Japanese patients with advanced solid tumours refractory to standard therapy or for which no standard therapy exists. The pharmacokinetics, pharmacodynamics and antitumour activity of MEDI-573 were also evaluated. Methods Three cohorts of patients received MEDI-573 in escalating order: cohort 1, 5 mg/kg on Day 1, 8 and 15; cohort 2, 15 mg/kg on Day 1, 8 and 15; cohort 3, 45 mg/kg on Day 1, of 21-day cycles. Results Ten patients who received at least one dose of MEDI-573 were evaluated. The median number of treatment cycles was 2.0 (range 1–6) and the median number of MEDI-573 doses received was 4.0 (range 1–17). The most commonly reported drug-related adverse events were fatigue (n = 2 patients), pyrexia (n = 2), diarrhoea (n = 2) and electrocardiogram QT prolongation (n = 2). No patients experienced a dose-limiting toxicity. Pharmacokinetics of MEDI-573 were linear with a dose-dependent increase. There were no complete or partial responses; four patients had an overall best response of stable disease. Conclusions MEDI-573 is well tolerated at the doses investigated.
KeywordsNovel antitumour agent IGF-II/I inhibitor MEDI-573 Monoclonal antibody Phase I Solid tumours
This study was sponsored by AstraZeneca. Writing assistance was provided by Claire Routley, PhD, from Mudskipper Business Ltd, funded by AstraZeneca.
Conflicts of interest
Tomohiro Nishina, Naoyuki Nogami, Yumiko Yamagiwa and Haruo Iguchi have no conflicts of interest to declare. Toshiyuki Kozuki has received honoraria from AstraZeneca KK. Katsuro Yagawa is an employee of AstraZeneca KK.
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