Personalized Breast Cancer Vaccine Safe in Early Trial

SAN FRANCISCO -- A personalized therapeutic vaccine breast cancer vaccine was safe and well tolerated when tested in 18 women with metastatic disease overexpressing HER-2, reported researchers here.

SAN FRANCISCO, Aug. 22 -- A personalized therapeutic breast cancer vaccine was safe and well tolerated when tested in 18 women with metastatic disease overexpressing HER-2, found researchers here.

In the phase 1 trial of the vaccine, lapuleucel-T (APC8024), there were tumor responses in one woman and disease stabilization in three, John W. Park, M.D., of the University of California San Francisco, and colleagues, reported in the Aug. 20 issue of the Journal of Clinical Oncology.

Lymphocyte proliferation and interferon gamma enzyme-linked immunospot assay detected "significant cellular immune responses specific for the immunizing antigen and HER-2 sequences were induced after treatment," they wrote.

All patients were required to have received prior treatment with trastuzumab (Herceptin), the drug that has shown a survival advantage for women with HER-2-positive tumors. Trastuzumab must have been discontinued six weeks before enrollment.

The autologous vaccine consists of peripheral blood mononuclear cells, which are obtained from patients by leukapheresis and activated in vitro with a recombinant fusion protein (BA7072 linked to GM-CSF). These activated cells including antigen-presenting cells are then re-infused intravenously into the patients.

The treatment regimen consisted of three biweekly leukaphereses and infusions. Each infusion was prepared from a single leukapheresis. The infusions were administered in escalated cell dose levels: 2 X 108, 1 X109, and 5 X 109.

Patients underwent physical examination and laboratory testing at baseline, and at two, four, eight, and 12 weeks, and at eight-week intervals thereafter.

Among the findings:

  • Six patients were treated at dose level 1 (2 X 108), eight patients were treated at dose level 2 (1 X109), and four patients were treated at dose level 3 (5 X 109).
  • Pyrexes developed in 14 patients and rigors in 11 patients.
  • Lapuleucel-T treatment was associated with a significant increase in proliferative response to either BA7072 (P=0.0195) or HER500 (P=0.0371) at week four and at week eight (BA7072, P=0.0029 or HER500 P=0.0137).
  • The median time to disease progression was 12.1 weeks (range 2.1 to 94.0+ weeks).
  • One woman had regression of a supraclavicular mass, which lasted for six months.
  • Three women had stable disease for at least a year.

"These results confirmed that this active cellular immunotherapy approach is feasible in advanced breast cancer patients who were able to receive immunologically active vaccination derived from autologous pheresis product," the investigators wrote.

The vaccine is being developed by Dendreon Corporation of Seattle, which is seeking FDA approval of a similar vaccine for prostate cancer. The prostate vaccine, set to be marketed as Provenge, was accepted for FDA fast track review in January after two clinical trials provided evidence that the vaccine stabilized the disease. But the FDA has delayed approval pending evidence that the vaccine can extend survival.