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Phase 1b Study of Trebananib Plus Paclitaxel and Trastuzumab in Patients With HER2-Positive Locally Recurrent or

Peter A Kaufman1, Hans Wildiers2, Gilles Freyer3

  • 1Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center, Lebanon, NH.

Clinical Breast Cancer
|November 14, 2018
PubMed
Abstract

Insights

Trebananib, combined with trastuzumab and paclitaxel, showed manageable side effects in a phase 1b study for HER2-positive breast cancer. The combination demonstrated anticancer activity, with objective responses observed in most patients.

Area of Science:

  • Oncology
  • Pharmacology
  • Biotechnology

Background:

  • Trebananib is a peptide-Fc fusion protein that inhibits angiogenesis by blocking angiopoietin-1/2 binding to the Tie2 receptor tyrosine kinase.
  • Angiogenesis plays a critical role in tumor growth and metastasis.
  • Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is an aggressive subtype often requiring targeted therapies.

Purpose of the Study:

  • To evaluate the safety and tolerability of trebananib in combination with trastuzumab and paclitaxel in patients with HER2-positive breast cancer.
  • To assess the preliminary efficacy of this combination therapy in terms of objective response and duration of response.
  • To determine the recommended dose for future clinical trials.

Main Methods:

  • An open-label, phase 1b clinical study was conducted.
  • Forty women with HER2-positive breast cancer were enrolled.
  • Patients received weekly paclitaxel, trastuzumab, and escalating doses of intravenous trebananib (10 mg/kg or 30 mg/kg).
  • Primary endpoint was dose-limiting toxicities; secondary endpoints included adverse events, pharmacokinetics, and tumor response.

Main Results:

  • Two patients experienced dose-limiting toxicities (grade 3 ocular transient ischemic attack and grade 3 elevated γ-glutamyl transferase).
  • The most common treatment-emergent adverse events were peripheral edema, diarrhea, alopecia, fatigue, and nausea.
  • Objective response was observed in 31 patients (77.5%), with partial responses in both dose cohorts and complete responses in the 30 mg/kg cohort.
  • Median duration of response was 12.6 months in the 10 mg/kg cohort and 16.6 months in the 30 mg/kg cohort.

Conclusions:

  • Trebananib, at doses up to 30 mg/kg weekly, was tolerated with manageable adverse events when combined with trastuzumab and paclitaxel.
  • The combination demonstrated anticancer activity, supporting further investigation in HER2-positive breast cancer.
  • The results support the continued development of trebananib as a targeted therapy for angiogenesis in cancer treatment.
Keywords:
AMG 386AngiogenesisAngiopoietinHER2 positive

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