An open-label, phase 2 trial of RPI.4610 (angiozyme) in the treatment of metastatic breast cancer

Phuong Khanh Morrow, Rashmi K. Murthy, Joe D. Ensor, Gilad S. Gordon, Kim A. Margolin, Anthony D. Elias, Walter J. Urba, David E. Weng, Hope S. Rugo, Gabriel N. Hortobagyi

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Background: Serum and plasma levels of vascular endothelial growth factor (VEGF) correlate with prognosis in patients with metastatic breast cancer (MBC). VEGF binds to 2 receptors on endothelial cells, VEGFR-1 and VEGFR-2. RPI.4610 (Angiozyme0) is an antiangiogenic ribozyme targeting the VEGFR-1 mRNA. Preclinical and phase 1 studies suggested that RPI.4610 is a well-tolerated agent with clinical activity in solid tumors. The authors' trial evaluated the efficacy of RPI.4610 in the treatment of patients with progressive MBC. Methods: This phase 2, multicenter, single-arm study was designed to assess the objective response rate of RPI.4610 in patients with MBC who had experienced disease progression with at least 1 course of chemotherapy for MBC. Patients received daily subcutaneous injections of RPI.4610 100 mg/m 2 for 12 weeks. Results: Most patients (93%) had received at least 2 lines of chemotherapy previously; 69% of patients had received at least 3 lines of chemotherapy. Median follow-up was 2.76 months (range, 0.89-36.6 months). No partial responses nor complete responses were found. Median progression-free survival was 1.41 months (95% confidence interval [CI], 1.35-1.45). The median overall survival from start of treatment was 11.89 months (95% CI, 4.11-23.66). Treatment-related adverse events (AEs) were primarily grade 1 to 2 in intensity. Most common AEs were: injection site reactions, abdominal pain, anorexia, chromaturia, constipation, dyspnea, fatigue, headache, pain at the injection site, nausea, vomiting, and fever. Conclusions: Although RPI.4610 demonstrated a well-tolerated safety profile, its lack of clinical efficacy precludes this drug from further development.

Original languageEnglish (US)
Pages (from-to)4098-4104
Number of pages7
Issue number17
StatePublished - Sep 1 2012


  • Angiozyme
  • RPI
  • metastatic breast cancer
  • phase 2
  • vascular endothelial growth factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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