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

Prema P. Peethambaram, Michelle E. Melisko, Kristine J. Rinn, Steven Robert Alberts, Nicole M. Provost, Lori A. Jones, Robert B. Sims, Lisa R C Lin, Mark W. Frohlich, John W. Park

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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-γ 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 immuneresponse 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.

Original languageEnglish (US)
Pages (from-to)5937-5944
Number of pages8
JournalClinical Cancer Research
Volume15
Issue number18
DOIs
StatePublished - Sep 15 2009

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Immunotherapy
Neoplasms
Active Immunotherapy
Antigens
Ovarian Neoplasms
Colorectal Neoplasms
Breast Neoplasms
Leukapheresis
Enzyme-Linked Immunospot Assay
Lapuleucel-T
Antigen-Presenting Cells
Therapeutics
Granulocyte-Macrophage Colony-Stimulating Factor
Blood Cells
Research Design
T-Lymphocytes
Safety

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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A phase I trial of immunotherapy with lapuleucel-T (APC8024) in patients with refractory metastatic tumors that express HER-2/neu. / Peethambaram, Prema P.; Melisko, Michelle E.; Rinn, Kristine J.; Alberts, Steven Robert; Provost, Nicole M.; Jones, Lori A.; Sims, Robert B.; Lin, Lisa R C; Frohlich, Mark W.; Park, John W.

In: Clinical Cancer Research, Vol. 15, No. 18, 15.09.2009, p. 5937-5944.

Research output: Contribution to journalArticle

Peethambaram, PP, Melisko, ME, Rinn, KJ, Alberts, SR, Provost, NM, Jones, LA, Sims, RB, Lin, LRC, Frohlich, MW & Park, JW 2009, 'A phase I trial of immunotherapy with lapuleucel-T (APC8024) in patients with refractory metastatic tumors that express HER-2/neu', Clinical Cancer Research, vol. 15, no. 18, pp. 5937-5944. https://doi.org/10.1158/1078-0432.CCR-08-3282
Peethambaram, Prema P. ; Melisko, Michelle E. ; Rinn, Kristine J. ; Alberts, Steven Robert ; Provost, Nicole M. ; Jones, Lori A. ; Sims, Robert B. ; Lin, Lisa R C ; Frohlich, Mark W. ; Park, John W. / A phase I trial of immunotherapy with lapuleucel-T (APC8024) in patients with refractory metastatic tumors that express HER-2/neu. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 18. pp. 5937-5944.
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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-γ 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 immuneresponse 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.",
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AU - Melisko, Michelle E.

AU - Rinn, Kristine J.

AU - Alberts, Steven Robert

AU - Provost, Nicole M.

AU - Jones, Lori A.

AU - Sims, Robert B.

AU - Lin, Lisa R C

AU - Frohlich, Mark W.

AU - Park, John W.

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N2 - 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-γ 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 immuneresponse 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.

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