A phase I trial of immunotherapy with lapuleucel-T (APC8024) in patients with refractory metastatic tumors that express HER-2/neu

Clin Cancer Res. 2009 Sep 15;15(18):5937-44. doi: 10.1158/1078-0432.CCR-08-3282. Epub 2009 Sep 1.

Abstract

Purpose: This study aimed to evaluate the safety of, immune response induced by, and efficacy of treatment with lapuleucel-T (APC8024) in patients with HER-2/neu-expressing tumors. Lapuleucel-T is an investigational active immunotherapy product consisting of autologous peripheral blood mononuclear cells, including antigen presenting cells, which are cultured ex vivo with BA7072, a recombinant fusion antigen consisting of portions of the intracellular and extracellular regions of HER-2/neu linked to granulocyte-macrophage colony-stimulating factor.

Experimental design: Patients with metastatic breast, ovarian, or colorectal cancer whose tumors expressed HER-2 were eligible. Patients underwent leukapheresis in week 0 and received lapuleucel-T infusions in weeks 0, 2, and 4. Patients who achieved a partial response or had stable disease through week 48 were eligible for re-treatment using the same protocol and dose as their initial treatment.

Results: Eighteen patients were enrolled and treated. Patients showed an immune response to the immunizing antigen (BA7072) at week 8 compared with week 0 as measured by T lymphocyte proliferation and IFN-gamma enzyme-linked immunospot assay. Therapy was well tolerated. The majority (94.7%) of adverse events associated with treatment were grade 1 or 2. Two patients experienced stable disease lasting > 48 weeks.

Conclusions: Autologous active cellular immunotherapy with lapuleucel-T stimulated an immune response specific to the immunizing antigen and seemed to be well tolerated. Further clinical studies to assess the clinical benefit for patients with HER/2-neu-expressing breast, ovarian, and colorectal cancer are warranted.

Publication types

  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / immunology
  • Breast Neoplasms / secondary
  • Breast Neoplasms / therapy*
  • Cancer Vaccines / immunology*
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / secondary
  • Colorectal Neoplasms / therapy*
  • Female
  • Humans
  • Immunotherapy*
  • Male
  • Middle Aged
  • Ovarian Neoplasms / immunology
  • Ovarian Neoplasms / secondary
  • Ovarian Neoplasms / therapy*
  • Receptor, ErbB-2 / biosynthesis*
  • Receptor, ErbB-2 / blood
  • Receptor, ErbB-2 / immunology

Substances

  • Cancer Vaccines
  • Lapuleucel-T
  • ERBB2 protein, human
  • Receptor, ErbB-2