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Phase 1/2 dose-escalation study of a GM-CSF-secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer†

  1. Celestia S. Higano MD1,‡,*,
  2. John M. Corman MD2,
  3. David C. Smith MD3,
  4. Arthur S. Centeno MD4,
  5. Christopher P. Steidle MD5,
  6. Marc Gittleman MD6,
  7. Jonathan W. Simons MD7,§,
  8. Natalie Sacks MD8,¶,
  9. Junko Aimi PhD8,¶,
  10. Eric J. Small MD9

Article first published online: 21 JUL 2008

DOI: 10.1002/cncr.23669

Issue

Cancer

Cancer

Volume 113, Issue 5, pages 975–984, 1 September 2008

Additional Information

How to Cite

Higano, C. S., Corman, J. M., Smith, D. C., Centeno, A. S., Steidle, C. P., Gittleman, M., Simons, J. W., Sacks, N., Aimi, J. and Small, E. J. (2008), Phase 1/2 dose-escalation study of a GM-CSF-secreting, allogeneic, cellular immunotherapy for metastatic hormone-refractory prostate cancer. Cancer, 113: 975–984. doi: 10.1002/cncr.23669

Author Information

  1. 1

    Departments of Oncology and Urology, University of Washington, Seattle, Seattle, Washington

  2. 2

    Floyd and Delores Jones Cancer Center, Virginia Mason Medical Center, Seattle, Washington

  3. 3

    Departments of Internal Medicine and Urology, University of Michigan Medical Center, Ann Arbor, Michigan

  4. 4

    Urology San Antonio, San Antonio, Texas

  5. 5

    Northeast Indiana Research, Fort Wayne, Indiana

  6. 6

    South Florida Medical Research, Aventura, Florida

  7. 7

    Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia

  8. 8

    Department of Clinical Research, Cell Genesys, Inc, South San Francisco, California

  9. 9

    Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California

  1. ‡

    Fax: (650) 595-0180

  2. §

    J.W. Simons is a coinventor of 2 issued US patents (US Pat. Nos. 7,226,606 and 7,217,421), has pending applications that are exclusively licensed to and co-owned by Cell Genesys, and has received honoraria from Cell Genesys for speaking engagements.

  3. N. Sacks and J. Aimi are employees of Cell Genesys.

*Seattle Cancer Care Alliance, 825 Eastlake Ave. E, P.O. Box 19023, Seattle, WA 98109-1023

  1. †

    All patients provided informed consent.

Publication History

  1. Issue published online: 20 AUG 2008
  2. Article first published online: 21 JUL 2008
  3. Manuscript Accepted: 11 APR 2008
  4. Manuscript Revised: 9 APR 2008
  5. Manuscript Received: 14 DEC 2007

Funded by

  • Cell Genesys, South San Francisco, California, to each investigator

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Keywords:

  • immunotherapy;
  • granulocyte-macrophage-colony-stimulating factor;
  • hormone-refractory prostate cancer;
  • treatment;
  • clinical trial;
  • GVAX

This open-label, multicenter, dose-escalation study evaluated a GM-CSF-secreting, cellular immunotherapy in 80 patients with metastatic hormone-refractory prostate cancer. Treatment was well tolerated and demonstrated immunogenicity and clinical activity. Phase 3 trials are underway.

Abstract

BACKGROUND

This open-label, multicenter, dose-escalation study evaluated multiple dose levels of immunotherapy in patients with metastatic hormone-refractory prostate cancer (HRPC). The immunotherapy, based on the GVAX platform, consisted of 2 allogeneic prostate-carcinoma cell lines modified to secrete granulocyte-macrophage-colony-stimulating factor (GM-CSF).

METHODS

Dose levels ranged from 100 × 106 cells q28d × 6 to 500 × 106 cells prime/300 × 106 cells boost q14d × 11. Endpoints included safety, immunogenicity, overall survival, radiologic response, prostate-specific antigen (PSA) kinetics, and serum GM-CSF pharmacokinetics.

RESULTS

Eighty men, median age 69 years (range, 49-90 years), were treated. The most common adverse effect was injection-site erythema. Overall, the immunotherapy was well tolerated. A maximal tolerated dose was not established. The median survival time was 35.0 months in the high-dose group, 20.0 months in the mid-dose, group, and 23.1 months in the low-dose group. PSA stabilization occurred in 15 (19%) patients, and a >50% decline in PSA was seen in 1 patient. The proportion of patients who generated an antibody response to 1 or both cell lines increased with dose and included 10 of 23 (43%) in the low-dose group, 13 of 18 (72%) in the mid-dose group, and 16 of 18 (89%) in the high-dose group (P = .002; Cochran-Armitage trend test).

CONCLUSIONS

This immunotherapy was well tolerated. Immunogenicity and overall survival varied by dose. Two phase 3 trials in patients with metastatic HRPC are underway. Cancer 2008. © 2008 American Cancer Society.

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