Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: Safety, clinical activity, pharmacodynamics, and immunologic correlates

Journal of Clinical Oncology

Volumn 28, Issue 19, 2010, Pages 3167-3175

  Brahmer, Julie R ^a   Drake, Charles G ^a   Wollner, Ira ^a   Powderly, John D ^a   Picus, Joel ^a   Sharfman, William H ^a   Stankevich, Elizabeth ^a   Pons, Alice ^a   Salay, Theresa M ^a   McMiller, Tracee L ^a   Gilson, Marta M ^a   Wang, Changyu ^a   Selby, Mark ^a   Taube, Janis M ^a   Anders, Robert ^a   Chen, Lieping ^a   Korman, Alan J ^a   Pardoll, Drew M ^a   Lowy, Israel ^a   Topalian, Suzanne L ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

MDX 1106; MONOCLONAL ANTIBODY; PROGRAMMED DEATH 1 RECEPTOR; UNCLASSIFIED DRUG; APOPTOSIS REGULATORY PROTEIN; LEUKOCYTE ANTIGEN; MDX-1106; PDCD1 PROTEIN, HUMAN;

ADULT; AGED; ANTINEOPLASTIC ACTIVITY; ARTICLE; CD4 LYMPHOCYTE COUNT; CLINICAL ARTICLE; COLITIS; COLORECTAL CANCER; DRUG DOSE ESCALATION; DRUG HALF LIFE; DRUG TOLERABILITY; FATIGUE; FEMALE; HUMAN; HYPOTHYROIDISM; KIDNEY CARCINOMA; LUNG NON SMALL CELL CANCER; LYMPHOCYTOPENIA; MALE; MELANOMA; MUSCULOSKELETAL DISEASE; PHASE 1 CLINICAL TRIAL; POLYARTHRITIS; PRIORITY JOURNAL; PROSTATE CANCER; SIDE EFFECT; SOLID TUMOR; TREATMENT RESPONSE; TUMOR REGRESSION; CHEMICALLY INDUCED DISORDER; CLINICAL TRIAL; COLORECTAL TUMOR; DOSE RESPONSE; IMMUNOLOGY; KIDNEY TUMOR; LUNG TUMOR; MIDDLE AGED; MULTICENTER STUDY; NEOPLASM; PATHOLOGY; PROSTATE TUMOR; TREATMENT OUTCOME;

ADULT; AGED; AGED, 80 AND OVER; ANTIBODIES, MONOCLONAL; ANTIGENS, CD; APOPTOSIS REGULATORY PROTEINS; CARCINOMA, NON-SMALL-CELL LUNG; CARCINOMA, RENAL CELL; COLORECTAL NEOPLASMS; DOSE-RESPONSE RELATIONSHIP, DRUG; FATIGUE; FEMALE; HUMANS; KIDNEY NEOPLASMS; LUNG NEOPLASMS; LYMPHOPENIA; MALE; MELANOMA; MIDDLE AGED; NEOPLASMS; PROSTATIC NEOPLASMS; TREATMENT OUTCOME;

EID: 77954899030     PISSN: 0732183X     EISSN: 15277755     Source Type: Journal    
DOI: 10.1200/JCO.2009.26.7609     Document Type: Article

References (19)

1. Segal NH, Parsons DW, Peggs KS, et al: Epitope landscape in breast and colorectal cancer. Cancer Res 68:889-892, 2008 (Pubitemid 351206767)
2. Smyth MJ, Dunn GP, Schreiber RD: Cancer immunosurveillance and immunoediting: The roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol 90:1-50, 2006 (Pubitemid 43765795)
3. Topalian SL, Chen L, Taube J, et al: Immunology, in Balch C, Houghton AN, Sober AJ, et al (eds): Cutaneous Melanoma (ed 5). St. Louis, MO, Quality Medical Publishing, 2009, pp 865-882
4. Waterhouse P, Penninger JM, Timms E, et al: Lymphoproliferative disorders with early lethality in mice deficient in CTLA-4. Science 270:985-988, 1995
5. Attia P, Phan GQ, Maker AV, et al: Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol 23:6043-6053, 2005
6. Keir ME, Butte MJ, Freeman GJ, et al: PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol 26:677-704, 2008 (Pubitemid 351600389)
7. Nishimura H, Nose M, Hiai H, et al: Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity 11:141-151, 1999 (Pubitemid 29428807)
8. Nishimura H, Okazaki T, Tanaka Y, et al: Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291:319-322, 2001 (Pubitemid 32096320)
9. Iwai Y, Ishida M, Tanaka Y, et al: Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A 99:12293-12297, 2002
10. Strome SE, Dong H, Tamura H, et al: B7-H1 blockade augments T-cell immunotherapy for squamous cell carcinoma. Cancer Res 63:6501-6505, 2003 (Pubitemid 37255203)
11. Blank C, Brown I, Peterson AC, et al: PD-L1/B7-H1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res 64:1140-1145, 2004 (Pubitemid 38176921)
12. Dong H, Strome SE, Salomao DR, et al: Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nature Med 8:793-800, 2002
13. Thompson RH, Kuntz SM, Leibovich BC, et al: Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res 66:3381-3385, 2006
14. Hamanishi J, Mandai M, Iwasaki M, et al: Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc Natl Acad Sci U S A 104:3360-3365, 2007 (Pubitemid 46364164)
15. Wong RM, Scotland RR, Lau RL, et al: Programmed death-1 blockade enhances expansion and functional capacity of human melanoma antigen-specific CTLs. Int Immunol 19:1223-1234, 2007 (Pubitemid 47500645)
16. Tsushima F, Yao S, Shin T, et al: Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy. Blood 110:180-185, 2007 (Pubitemid 47026833)
17. Goldberg MV, Maris CH, Hipkiss EL, et al: Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells. Blood 110:186-192, 2007 (Pubitemid 47026834)
18. Berger R, Rotem-Yehudar R, Slama G, et al: Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res 14:3044-3051, 2008
19. Li B, VanRoey M, Wang C, et al: Anti-programmed death-1 synergizes with granulocyte macrophage colony-stimulating factor-secreting tumor cell immunotherapy providing therapeutic benefit to mice with established tumors. Clin Cancer Res 15:1623-1634, 2009