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A phase I trial of the trifunctional anti Her2 × anti CD3 antibody ertumaxomab in patients with advanced solid tumors.

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اقرأ على الانترنت اقرأ أكثر حفظ في قائمتي
  • معلومة اضافية
    • المصدر:
      Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE
    • بيانات النشر:
      Original Publication: London : BioMed Central, [2001-
    • الموضوع:
      Antibodies, Monoclonal/*administration & dosage ; Breast Neoplasms/*drug therapy ; Rectal Neoplasms/*drug therapy ; Stomach Neoplasms/*drug therapy; Administration, Intravenous ; Adult ; Aged ; Antibodies, Monoclonal/adverse effects ; Breast Neoplasms/metabolism ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Female ; Humans ; Male ; Maximum Tolerated Dose ; Middle Aged ; Receptor, ErbB-2/metabolism ; Rectal Neoplasms/metabolism ; Stomach Neoplasms/metabolism ; Treatment Outcome
    • نبذة مختصرة :
      Background: Ertumaxomab (ertu) is a bispecific, trifunctional antibody targeting Her2/neu, CD3 and the Fcγ-receptors I, IIa, and III forming a tri-cell complex between tumor cell, T cell and accessory cells.
      Methods: Patients (pts) with Her2/neu (1+/SISH positive, 2+ and 3+) expressing tumors progressing after standard therapy were treated to investigate safety, tolerability and preliminary efficacy. In this study, ertu was applied i.v. in 2 cycles following a predefined dose escalating scheme. Each cycle consisted of five ascending doses (10-500 μg) applied weekly within 28 days with a 21 day treatment-free interval. If 2 pts experienced a dose limiting toxicity (DLT) at a given dose level, the maximum tolerated dose (MTD) had been exceeded.
      Results: Fourteen heavily pretreated pts (e.g. breast, rectal, gastric cancer) were enrolled in the four main cohorts. Three (21 %) pts had to be replaced. Two serious adverse events (SAE) with possible relation to the investigational drug were seen, both fully reversible. A DLT was not detected. Consequently, the MTD could not be determined. All adverse events (AE) were transient and completely reversible. Most frequent AEs were fatigue (14/14), pain (13/14), cephalgia (12/14), chills (11/14), nausea (8/14), fever (7/14), emesis (7/14) and diarrhea (5/14). Single doses up to 300 μg were well tolerated (total dose up to 800 μg per cycle). We observed one partial remission and two disease stabilizations after first treatment cycle.
      Conclusions: Single doses up to 300 μg could be safely administered in an escalating dose scheme. Immunological responses and clinical activity warrant further evaluation in patients with Her2 over expressing tumors.
      Trial Registration: EudraCT number: 2011-003201-14; ClinicalTrials.gov identifier: NCT01569412.
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    • Contributed Indexing:
      Keywords: Advanced cancer; Dose escalation; Dose limiting toxicity; Ertumaxomab; Her2/neu; Maximum tolerated dose
    • Molecular Sequence:
      ClinicalTrials.gov NCT01569412
    • الرقم المعرف:
      0 (Antibodies, Monoclonal)
      EC 2.7.10.1 (ERBB2 protein, human)
      EC 2.7.10.1 (Receptor, ErbB-2)
      L5L45YGP1O (ertumaxomab)
    • الموضوع:
      Date Created: 20160709 Date Completed: 20171003 Latest Revision: 20190107
    • الموضوع:
      20250114
    • الرقم المعرف:
      PMC4937525
    • الرقم المعرف:
      10.1186/s12885-016-2449-0
    • الرقم المعرف:
      27387446