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Haluska P , Menefee M , Plimack ER , Rosenberg J , Northfelt D , LaVallee T , Shi L , Yu XQ , Burke P , Huang J , Viner J , McDevitt J , LoRusso P
Phase I dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors
Clin Cancer Res. 2014 Sep 15;20(18) :4747-57
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Abstract
PURPOSE: This phase I, multicenter, open-label, single-arm, dose-escalation, and dose-expansion study evaluated the safety, tolerability, and antitumor activity of MEDI-573 in adults with advanced solid tumors refractory to standard therapy or for which no standard therapy exists. EXPERIMENTAL DESIGN: Patients received MEDI-573 in 1 of 5 cohorts (0.5, 1.5, 5, 10, or 15 mg/kg) dosed weekly or 1 of 2 cohorts (30 or 45 mg/kg) dosed every 3 weeks. Primary end points included the MEDI-573 safety profile, maximum tolerated dose (MTD), and optimal biologic dose (OBD). Secondary end points included MEDI-573 pharmacokinetics (PK), pharmacodynamics, immunogenicity, and antitumor activity. RESULTS: In total, 43 patients (20 with urothelial cancer) received MEDI-573. No dose-limiting toxicities were identified, and only 1 patient experienced hyperglycemia related to treatment. Elevations in levels of insulin and/or growth hormone were not observed. Adverse events observed in >10% of patients included fatigue, anorexia, nausea, diarrhea, and anemia. PK evaluation demonstrated that levels of MEDI-573 increased with dose at all dose levels tested. At doses >5 mg/kg, circulating levels of insulin-like growth factor (IGF)-I and IGFII were fully suppressed. Of 39 patients evaluable for response, none experienced partial or complete response and 13 had stable disease as best response. CONCLUSIONS: The MTD of MEDI-573 was not reached. The OBD was 5 mg/kg weekly or 30 or 45 mg/kg every 3 weeks. MEDI-573 showed preliminary antitumor activity in a heavily pretreated population and had a favorable tolerability profile, with no notable perturbations in metabolic homeostasis.
Notes
Haluska, Paul Menefee, Michael Plimack, Elizabeth R Rosenberg, Jonathan Northfelt, Donald LaVallee, Theresa Shi, Li Yu, Xiang-Qing Burke, Patricia Huang, Jaiqi Viner, Jaye McDevitt, Jennifer LoRusso, Patricia Journal Article Research Support, Non-U.S. Gov't United States Clin Cancer Res. 2014 Sep 15;20(18):4747-57. doi: 10.1158/1078-0432.CCR-14-0114. Epub 2014 Jul 14.