Advertisement
Journal of Clinical Oncology  
Search for:
Limit by:
  Browse by Subject or Issue
Home Search or Browse JCO My JCO Subscriptions Customer Service Site Map

Originally published as JCO Early Release 10.1200/JCO.2005.01.109 on October 3 2005

Journal of Clinical Oncology, Vol 23, No 35 (December 10), 2005: pp. 8968-8977
© 2005 American Society of Clinical Oncology.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Save to my personal folders
Right arrow Download to citation manager
Right arrowRights & Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ribas, A.
Right arrow Articles by Gomez-Navarro, J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ribas, A.
Right arrow Articles by Gomez-Navarro, J.
Related Articles
Right arrowRelated Editorial
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

Antitumor Activity in Melanoma and Anti-Self Responses in a Phase I Trial With the Anti-Cytotoxic T Lymphocyte–Associated Antigen 4 Monoclonal Antibody CP-675,206

Antoni Ribas, Luis H. Camacho, Gabriel Lopez-Berestein, Dmitri Pavlov, Cecile A. Bulanhagui, Robert Millham, Begoña Comin-Anduix, James M. Reuben, Elisabeth Seja, Charla A. Parker, Amarnath Sharma, John A. Glaspy, Jesus Gomez-Navarro

From the Departments of Medicine, Division of Hematology/Oncology; Surgery, Division of Surgical Oncology and UCLA Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA; Departments of Experimental Therapeutics, Melanoma Medical Oncology and Hematopathology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; and Pfizer Global Research and Development, Groton-New London, CT

Address reprint requests to Luis H. Camacho, MD, MPH, Phase I Program/Division of Cancer Medicine, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 422, Houston, TX 77030; e-mail: lhcamacho{at}mdanderson.org.

PURPOSE: Cytotoxic T lymphocyte–associated antigen 4 (CTLA4) blockade with CP-675,206, a fully human anti-CTLA4 monoclonal antibody, may break peripheral immunologic tolerance leading to effective immune responses to cancer in humans. A phase I trial was conducted to test the safety of CP-675,206.

PATIENTS AND METHODS: Thirty-nine patients with solid malignancies (melanoma, n = 34; renal cell, n = 4; colon, n = 1) received an intravenous (IV) infusion of CP-675,206 at seven dose levels. The primary objective was to determine the maximum-tolerated dose and the recommended phase II dose.

RESULTS: Dose-limiting toxicities and autoimmune phenomena included diarrhea, dermatitis, vitiligo, panhypopituitarism and hyperthyroidism. Two patients experienced complete responses (maintained for 34+ and 25+ months), and there were two partial responses (26+ and 25+ months) among 29 patients with measurable melanoma. There have been no relapses thus far after objective response to therapy. Four other patients had stable disease at end of study evaluation (16, 7, 7, and 4 months). Additionally, five patients had extended periods without disease progression (36+, 35+, 26+, 24+, and 23+ months) after local treatment of progressive metastases. Longer systemic exposure to CP-675,206 achieved in higher dose cohorts predicted for a higher probability of response.

CONCLUSION: CP-675,206 can be administered safely to humans as a single IV dose up to 15 mg/kg, resulting in breaking of peripheral immune tolerance to self-tissues and antitumor activity in melanoma.

Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.

Terms in blue are defined in the glossary, found at the end of this issue and online at www.jco.org.

Authors' disclosures of potential conflicts of interest are found at the end of this article.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related Editorial

  • CTLA-4 Blockade: Autoimmunity As Treatment
    Dilnawaz Kapadia and Lawrence Fong
    JCO 2005 23: 8926-8928 [Full Text]


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
A. Ribas, B. Comin-Anduix, B. Chmielowski, J. Jalil, P. de la Rocha, T. A. McCannel, M. T. Ochoa, E. Seja, A. Villanueva, D. K. Oseguera, et al.
Dendritic Cell Vaccination Combined with CTLA4 Blockade in Patients with Metastatic Melanoma
Clin. Cancer Res., October 1, 2009; 15(19): 6267 - 6276.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
K. S. Peggs, S. A. Quezada, C. A. Chambers, A. J. Korman, and J. P. Allison
Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies
J. Exp. Med., August 3, 2009; 206(8): 1717 - 1725.
[Abstract] [Full Text] [PDF]

Home page
 NDT PlusHome page
E. C. Jolly, M. R. Clatworthy, C. Lawrence, P. D. Nathan, and K. Farrington
Anti-CTLA-4 (CD 152) monoclonal antibody-induced autoimmune interstitial nephritis
NDT Plus, August 1, 2009; 2(4): 300 - 302.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. Lotem, A. Machlenkin, T. Hamburger, A. Nissan, L. Kadouri, S. Frankenburg, Z. Gimmon, O. Elias, I. B. David, A. Kuznetz, et al.
Autologous Melanoma Vaccine Induces Antitumor and Self-Reactive Immune Responses That Affect Patient Survival and Depend on MHC Class II Expression on Vaccine Cells
Clin. Cancer Res., August 1, 2009; 15(15): 4968 - 4977.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
C. Robert and F. Ghiringhelli
What Is the Role of Cytotoxic T Lymphocyte-Associated Antigen 4 Blockade in Patients with Metastatic Melanoma?
Oncologist, August 1, 2009; 14(8): 848 - 861.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
O. Klein, L. M. Ebert, T. Nicholaou, J. Browning, S. E. Russell, M. Zuber, H. M. Jackson, N. Dimopoulos, B. S. Tan, A. Hoos, et al.
Melan-A-specific Cytotoxic T Cells Are Associated with Tumor Regression and Autoimmunity Following Treatment with Anti-CTLA-4
Clin. Cancer Res., April 1, 2009; 15(7): 2507 - 2513.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
W. K. Nevala, C. M. Vachon, A. A. Leontovich, C. G. Scott, M. A. Thompson, S. N. Markovic, and for the Melanoma Study Group of the Mayo Clinic Ca
Evidence of Systemic Th2-Driven Chronic Inflammation in Patients with Metastatic Melanoma
Clin. Cancer Res., March 15, 2009; 15(6): 1931 - 1939.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
L. H. Camacho, S. Antonia, J. Sosman, J. M. Kirkwood, T. F. Gajewski, B. Redman, D. Pavlov, C. Bulanhagui, V. A. Bozon, J. Gomez-Navarro, et al.
Phase I/II Trial of Tremelimumab in Patients With Metastatic Melanoma
J. Clin. Oncol., March 1, 2009; 27(7): 1075 - 1081.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
A. Ribas, B. Comin-Anduix, J. S. Economou, T. R. Donahue, P. de la Rocha, L. F. Morris, J. Jalil, V. B. Dissette, I. P. Shintaku, J. A. Glaspy, et al.
Intratumoral Immune Cell Infiltrates, FoxP3, and Indoleamine 2,3-Dioxygenase in Patients with Melanoma Undergoing CTLA4 Blockade
Clin. Cancer Res., January 1, 2009; 15(1): 390 - 399.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. S. Weber, S. O'Day, W. Urba, J. Powderly, G. Nichol, M. Yellin, J. Snively, and E. Hersh
Phase I/II Study of Ipilimumab for Patients With Metastatic Melanoma
J. Clin. Oncol., December 20, 2008; 26(36): 5950 - 5956.
[Abstract] [Full Text] [PDF]

Home page
 Am J Health Syst PharmHome page
J. Poust
Targeting metastatic melanoma
Am. J. Health Syst. Pharm., December 15, 2008; 65(24_Supplement_9): S9 - S15.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
L. Fong and E. J. Small
Anti-Cytotoxic T-Lymphocyte Antigen-4 Antibody: The First in an Emerging Class of Immunomodulatory Antibodies for Cancer Treatment
J. Clin. Oncol., November 10, 2008; 26(32): 5275 - 5283.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
J. D. Wolchok and Y. Saenger
The Mechanism of Anti-CTLA-4 Activity and the Negative Regulation of T-Cell Activation
Oncologist, October 1, 2008; 13(suppl_4): 2 - 9.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
A. Ribas
Overcoming Immunologic Tolerance to Melanoma: Targeting CTLA-4 with Tremelimumab (CP-675,206)
Oncologist, October 1, 2008; 13(suppl_4): 10 - 15.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
J. Weber
Overcoming Immunologic Tolerance to Melanoma: Targeting CTLA-4 with Ipilimumab (MDX-010)
Oncologist, October 1, 2008; 13(suppl_4): 16 - 25.
[Abstract] [Full Text] [PDF]

Home page
 QJMHome page
J. King, J. Waxman, and H. Stauss
Advances in tumour immunotherapy
QJM, September 1, 2008; 101(9): 675 - 683.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. Menard, F. Ghiringhelli, S. Roux, N. Chaput, C. Mateus, U. Grohmann, S. Caillat-Zucman, L. Zitvogel, and C. Robert
CTLA-4 Blockade Confers Lymphocyte Resistance to Regulatory T-Cells in Advanced Melanoma: Surrogate Marker of Efficacy of Tremelimumab?
Clin. Cancer Res., August 15, 2008; 14(16): 5242 - 5249.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. L. Tang, J. R. Teijaro, M. N. Njau, S. S. Chandran, A. Azimzadeh, S. G. Nadler, D. M. Rothstein, and D. L. Farber
CTLA4 Expression Is an Indicator and Regulator of Steady-State CD4+FoxP3+ T Cell Homeostasis
J. Immunol., August 1, 2008; 181(3): 1806 - 1813.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
C. L-L. Chiang, J. A. Ledermann, E. Aitkens, E. Benjamin, D. R. Katz, and B. M. Chain
Oxidation of Ovarian Epithelial Cancer Cells by Hypochlorous Acid Enhances Immunogenicity and Stimulates T Cells that Recognize Autologous Primary Tumor
Clin. Cancer Res., August 1, 2008; 14(15): 4898 - 4907.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
J. M. Kirkwood, A. A. Tarhini, M. C. Panelli, S. J. Moschos, H. M. Zarour, L. H. Butterfield, and H. J. Gogas
Next Generation of Immunotherapy for Melanoma
J. Clin. Oncol., July 10, 2008; 26(20): 3445 - 3455.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
F. S. Hodi, M. Butler, D. A. Oble, M. V. Seiden, F. G. Haluska, A. Kruse, S. MacRae, M. Nelson, C. Canning, I. Lowy, et al.
Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients
PNAS, February 26, 2008; 105(8): 3005 - 3010.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
F. S. Hodi
Cytotoxic T-Lymphocyte Associated Antigen-4
Clin. Cancer Res., September 15, 2007; 13(18): 5238 - 5242.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
X. Zang and J. P. Allison
The B7 Family and Cancer Therapy: Costimulation and Coinhibition
Clin. Cancer Res., September 15, 2007; 13(18): 5271 - 5279.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
D. F. McDermott and M. B. Atkins
More Support for the Judicious Use of High-Dose Interleukin-2 in Patients With Advanced Melanoma
J. Clin. Oncol., September 1, 2007; 25(25): 3791 - 3793.
[Full Text] [PDF]

Home page
 Int ImmunolHome page
T. Okazaki and T. Honjo
PD-1 and PD-1 ligands: from discovery to clinical application
Int. Immunol., July 2, 2007; (2007) dxm057v1.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
J. Weber
Review: Anti CTLA-4 Antibody Ipilimumab: Case Studies of Clinical Response and Immune-Related Adverse Events
Oncologist, July 1, 2007; 12(7): 864 - 872.
[Abstract] [Full Text] [PDF]

Home page
 The OncologistHome page
A. Ribas, D. C. Hanson, D. A. Noe, R. Millham, D. J. Guyot, S. H. Bernstein, P. C. Canniff, A. Sharma, and J. Gomez-Navarro
Tremelimumab (CP-675,206), a Cytotoxic T Lymphocyte Associated Antigen 4 Blocking Monoclonal Antibody in Clinical Development for Patients with Cancer
Oncologist, July 1, 2007; 12(7): 873 - 883.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
A. Kretz-Rommel, F. Qin, N. Dakappagari, E. P. Ravey, J. McWhirter, D. Oltean, S. Frederickson, T. Maruyama, M. A. Wild, M.-J. Nolan, et al.
CD200 Expression on Tumor Cells Suppresses Antitumor Immunity: New Approaches to Cancer Immunotherapy
J. Immunol., May 1, 2007; 178(9): 5595 - 5605.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. A. Shaw, L. H. Camacho, I. E. McCutcheon, and S. G. Waguespack
Transient Hypophysitis after Cytotoxic T Lymphocyte-Associated Antigen 4 (CTLA4) Blockade
J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1201 - 1202.
[Full Text] [PDF]

Home page
 Mayo Clin Proc.Home page
S. N. Markovic, L. A. Erickson, R. D. Rao, R. H. Weenig, B. A. Pockaj, A. Bardia, C. M. Vachon, S. E. Schild, R. R. McWilliams, J. L. Hand, et al.
Malignant Melanoma in the 21st Century, Part 2: Staging, Prognosis, and Treatment
Mayo Clin. Proc., April 1, 2007; 82(4): 490 - 513.
[Abstract] [Full Text] [PDF]

Home page
 JCOHome page
R. H. Vonderheide, K. T. Flaherty, M. Khalil, M. S. Stumacher, D. L. Bajor, N. A. Hutnick, P. Sullivan, J. J. Mahany, M. Gallagher, A. Kramer, et al.
Clinical Activity and Immune Modulation in Cancer Patients Treated With CP-870,893, a Novel CD40 Agonist Monoclonal Antibody
J. Clin. Oncol., March 1, 2007; 25(7): 876 - 883.
[Abstract] [Full Text] [PDF]

Home page
 Ann OncolHome page
S. Danson and P. Lorigan
Melanoma vaccines - they should work
Ann. Onc., April 1, 2006; 17(4): 539 - 541.
[Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
M. B. Atkins
Cytokine-based therapy and biochemotherapy for advanced melanoma.
Clin. Cancer Res., April 1, 2006; 12(7): 2353s - 2358s.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
H. Koon and M. Atkins
Autoimmunity and Immunotherapy for Cancer
N. Engl. J. Med., February 16, 2006; 354(7): 758 - 760.
[Full Text] [PDF]

Home page
 JCOHome page
P. Sabbatini and D. R. Spriggs
Consolidation for Ovarian Cancer in Remission
J. Clin. Oncol., February 1, 2006; 24(4): 537 - 539.
[Full Text] [PDF]

Home page
 JCOHome page
D. Kapadia and L. Fong
CTLA-4 Blockade: Autoimmunity As Treatment
J. Clin. Oncol., December 10, 2005; 23(35): 8926 - 8928.
[Full Text] [PDF]


About
JCO		 Editorial
Roster		 Advertising
Information		 Librarians &
Institutions		 Rights &
Permissions		 PDA Services

Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
Terms and Conditions of Use
  HighWire Press HighWire Press™ assists in the publication of JCO Online