Phase i dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors

Paul Haluska, Michael Menefee, Elizabeth R. Plimack, Jonathan Rosenberg, Donald Northfelt, Theresa LaVallee, Li Shi, Xiang Qing Yu, Patricia Burke, Jaiqi Huang, Jaye Viner, Jennifer McDevitt, Patricia LoRusso

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32 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4747-4757
Number of pages11
JournalClinical Cancer Research
Volume20
Issue number18
DOIs
StatePublished - Sep 15 2014

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Haluska, P., Menefee, M., Plimack, E. R., Rosenberg, J., Northfelt, D., LaVallee, T., Shi, L., Yu, X. Q., Burke, P., Huang, J., Viner, J., McDevitt, J., & LoRusso, P. (2014). Phase i dose-escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. Clinical Cancer Research, 20(18), 4747-4757. https://doi.org/10.1158/1078-0432.CCR-14-0114