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

PubWeight™: 17.13‹?› | Rank: Top 0.1% | All-Time Top 10000

🔗 View Article (PMID 20516446)

Published in J Clin Oncol on June 01, 2010

Authors

Julie R Brahmer1, Charles G Drake, Ira Wollner, John D Powderly, Joel Picus, William H Sharfman, Elizabeth Stankevich, Alice Pons, Theresa M Salay, Tracee L McMiller, Marta M Gilson, Changyu Wang, Mark Selby, Janis M Taube, Robert Anders, Lieping Chen, Alan J Korman, Drew M Pardoll, Israel Lowy, Suzanne L Topalian

Author Affiliations

1: Johns Hopkins University School of Medicine, and the Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, USA.

Associated clinical trials:

A Phase 1 Study of Nivolumab (BMS-936558) in Subjects With Advanced or Recurrent Malignancies (MDX1106-03) | NCT00730639

A Study of MDX-1106 in Patients With Selected Refractory or Relapsed Malignancies (MDX1106-01) | NCT00441337

Articles citing this

(truncated to the top 100)

Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med (2012) 52.99

Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med (2012) 35.24

The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer (2012) 24.94

Comprehensive genomic characterization of squamous cell lung cancers. Nature (2012) 18.90

Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med (2013) 18.08

Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med (2012) 13.12

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med (2015) 13.08

Cancer immunotherapy comes of age. Nature (2011) 12.35

Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med (2015) 11.98

Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol (2014) 9.86

Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res (2014) 8.11

Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol (2012) 7.26

Cancer immunotherapy comes of age. J Clin Oncol (2011) 5.87

Up-regulation of PD-L1, IDO, and T(regs) in the melanoma tumor microenvironment is driven by CD8(+) T cells. Sci Transl Med (2013) 5.82

Antibody therapy of cancer. Nat Rev Cancer (2012) 5.17

Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell (2015) 5.10

Neutralizing tumor-promoting chronic inflammation: a magic bullet? Science (2013) 3.91

Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res (2011) 3.81

Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial. J Clin Oncol (2013) 3.77

Immunogenic cell death and DAMPs in cancer therapy. Nat Rev Cancer (2012) 3.76

Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res (2012) 3.68

Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res (2013) 3.48

Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res (2013) 3.27

Cancer immunology--analysis of host and tumor factors for personalized medicine. Nat Rev Clin Oncol (2011) 2.90

Evidence for a role of the PD-1:PD-L1 pathway in immune resistance of HPV-associated head and neck squamous cell carcinoma. Cancer Res (2013) 2.81

Nivolumab for Metastatic Renal Cell Carcinoma: Results of a Randomized Phase II Trial. J Clin Oncol (2014) 2.78

Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8+ T cell responses during chronic infection. Nat Immunol (2011) 2.76

Safety, efficacy, and biomarkers of nivolumab with vaccine in ipilimumab-refractory or -naive melanoma. J Clin Oncol (2013) 2.70

Breathing new life into immunotherapy: review of melanoma, lung and kidney cancer. Nat Rev Clin Oncol (2013) 2.64

Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat (2014) 2.61

Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses. Cell (2015) 2.60

Prostate cancer and inflammation: the evidence. Histopathology (2012) 2.60

A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol (2013) 2.50

Pseudoprogression and Immune-Related Response in Solid Tumors. J Clin Oncol (2015) 2.38

Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy. Proc Natl Acad Sci U S A (2011) 2.35

PD-L1 expression in the Merkel cell carcinoma microenvironment: association with inflammation, Merkel cell polyomavirus and overall survival. Cancer Immunol Res (2013) 2.30

Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab. J Clin Oncol (2015) 2.30

Anti-PD-1 blockade and stereotactic radiation produce long-term survival in mice with intracranial gliomas. Int J Radiat Oncol Biol Phys (2013) 2.28

Prostate cancer as a model for tumour immunotherapy. Nat Rev Immunol (2010) 2.28

Combination cancer immunotherapy and new immunomodulatory targets. Nat Rev Drug Discov (2015) 2.25

PD-1 blockade enhances T-cell migration to tumors by elevating IFN-γ inducible chemokines. Cancer Res (2012) 2.23

Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat Rev Cancer (2016) 2.19

The Impact of Tonsillectomy upon the Risk of Oropharyngeal Carcinoma Diagnosis and Prognosis in the Danish Cancer Registry. Cancer Prev Res (Phila) (2015) 2.17

PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Sci Transl Med (2016) 2.16

The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells. Immunology (2013) 2.14

Therapeutic cancer vaccines: current status and moving forward. J Natl Cancer Inst (2012) 2.09

Designing vaccines based on biology of human dendritic cell subsets. Immunity (2010) 2.04

Cross-talk between myeloid-derived suppressor cells (MDSC), macrophages, and dendritic cells enhances tumor-induced immune suppression. Semin Cancer Biol (2012) 2.01

PD-1 as a potential target in cancer therapy. Cancer Med (2013) 1.98

Anti-CTLA-4 antibody therapy: immune monitoring during clinical development of a novel immunotherapy. Semin Oncol (2010) 1.98

Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq. Science (2016) 1.95

Simultaneous blockade of multiple immune system inhibitory checkpoints enhances antitumor activity mediated by interleukin-15 in a murine metastatic colon carcinoma model. Clin Cancer Res (2010) 1.92

Therapeutic cancer vaccines: are we there yet? Immunol Rev (2011) 1.86

The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat (2013) 1.84

Extended co-expression of inhibitory receptors by human CD8 T-cells depending on differentiation, antigen-specificity and anatomical localization. PLoS One (2012) 1.77

The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma. Clin Ther (2015) 1.73

Overcoming T cell exhaustion in infection and cancer. Trends Immunol (2015) 1.72

Programmed death ligand 2 in cancer-induced immune suppression. Clin Dev Immunol (2012) 1.71

Immunotherapy earns its spot in the ranks of cancer therapy. J Exp Med (2012) 1.71

Anti-PD-1/PD-L1 therapy of human cancer: past, present, and future. J Clin Invest (2015) 1.67

Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol (2015) 1.65

Immunotherapy converts nonimmunogenic pancreatic tumors into immunogenic foci of immune regulation. Cancer Immunol Res (2014) 1.62

Human cancer immunotherapy with antibodies to the PD-1 and PD-L1 pathway. Trends Mol Med (2014) 1.59

Protein expression of programmed death 1 ligand 1 and ligand 2 independently predict poor prognosis in surgically resected lung adenocarcinoma. Onco Targets Ther (2014) 1.58

Ad3-hTERT-E1A, a fully serotype 3 oncolytic adenovirus, in patients with chemotherapy refractory cancer. Mol Ther (2012) 1.57

Therapy for metastatic melanoma: the past, present, and future. BMC Med (2012) 1.57

OX40 is a potent immune-stimulating target in late-stage cancer patients. Cancer Res (2013) 1.57

The changing therapeutic landscape of castration-resistant prostate cancer. Nat Rev Clin Oncol (2011) 1.55

Melanoma: new insights and new therapies. J Invest Dermatol (2012) 1.54

Restoring immune function of tumor-specific CD4+ T cells during recurrence of melanoma. J Immunol (2013) 1.53

PD-1/PD-L1 inhibitors. Curr Opin Pharmacol (2015) 1.53

B7 family checkpoint regulators in immune regulation and disease. Trends Immunol (2013) 1.53

Programmed death ligand 1 expression and tumor-infiltrating lymphocytes in glioblastoma. Neuro Oncol (2014) 1.53

Toxicities of Immunotherapy for the Practitioner. J Clin Oncol (2015) 1.50

Immune checkpoint inhibitors: making immunotherapy a reality for the treatment of lung cancer. Cancer Immunol Res (2013) 1.47

Advances in targeting cell surface signalling molecules for immune modulation. Nat Rev Drug Discov (2013) 1.46

T-cell invigoration to tumour burden ratio associated with anti-PD-1 response. Nature (2017) 1.46

Antagonists of PD-1 and PD-L1 in Cancer Treatment. Semin Oncol (2015) 1.45

Combining radiation and immunotherapy: a new systemic therapy for solid tumors? Cancer Immunol Res (2014) 1.43

Strength of PD-1 signaling differentially affects T-cell effector functions. Proc Natl Acad Sci U S A (2013) 1.42

PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells. J Clin Invest (2013) 1.42

Immunotherapy for prostate cancer: recent advances, lessons learned, and areas for further research. Clin Cancer Res (2011) 1.38

Clinical significance of tumor-associated inflammatory cells in metastatic neuroblastoma. J Clin Oncol (2012) 1.37

Role of the PD-1 pathway in the immune response. Am J Transplant (2012) 1.35

Antibody-based immunotherapy of cancer. Cell (2012) 1.35

PD-1/PD-L1 blockade together with vaccine therapy facilitates effector T-cell infiltration into pancreatic tumors. J Immunother (2015) 1.35

Trial Watch: Monoclonal antibodies in cancer therapy. Oncoimmunology (2012) 1.34

Induction of tumoricidal function in CD4+ T cells is associated with concomitant memory and terminally differentiated phenotype. J Exp Med (2012) 1.32

Immunology beats cancer: a blueprint for successful translation. Nat Immunol (2012) 1.32

Viral acute lower respiratory infections impair CD8+ T cells through PD-1. J Clin Invest (2012) 1.31

Monoclonal antibodies in cancer therapy. Cancer Immun (2012) 1.31

A new understanding in the epidemiology of melanoma. Expert Rev Anticancer Ther (2010) 1.30

Elevated serum soluble CD40 ligand in cancer patients may play an immunosuppressive role. Blood (2012) 1.30

Immune modulation of the tumor microenvironment for enhancing cancer immunotherapy. Oncoimmunology (2013) 1.29

Potential targets for pancreatic cancer immunotherapeutics. Immunotherapy (2011) 1.29

Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice. J Exp Med (2012) 1.29

Combination immune therapies to enhance anti-tumor responses by NK cells. Front Immunol (2013) 1.29

Cancer: Antitumour immunity gets a boost. Nature (2014) 1.28

Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging. Proc Natl Acad Sci U S A (2015) 1.26

Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes for metastatic melanoma: current status and future outlook. Cancer J (2012) 1.26

Articles cited by this

Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med (2002) 23.42

PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol (2008) 19.24

Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science (1995) 16.19

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 (2002) 12.39

Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity (1999) 12.36

Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol (2005) 9.72

Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science (2001) 8.31

Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res (2006) 8.21

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 (2007) 7.49

PD-L1/B7H-1 inhibits the effector phase of tumor rejection by T cell receptor (TCR) transgenic CD8+ T cells. Cancer Res (2004) 5.59

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 (2008) 5.50

Epitope landscape in breast and colorectal cancer. Cancer Res (2008) 5.29

Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol (2006) 4.98

B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res (2003) 3.96

Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy. Blood (2007) 3.00

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 (2009) 2.97

Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells. Blood (2007) 2.93

Programmed death-1 blockade enhances expansion and functional capacity of human melanoma antigen-specific CTLs. Int Immunol (2007) 2.67

Articles by these authors

Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med (2012) 52.99

Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med (2012) 35.24

Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med (2002) 23.42

Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med (2004) 22.96

Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science (2002) 19.77

Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med (2013) 17.53

Cancer regression in patients after transfer of genetically engineered lymphocytes. Science (2006) 16.96

A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med (2003) 14.59

Colocalization of inflammatory response with B7-h1 expression in human melanocytic lesions supports an adaptive resistance mechanism of immune escape. Sci Transl Med (2012) 13.12

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med (2015) 13.08

Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol (2005) 12.88

Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc Natl Acad Sci U S A (2003) 10.71

Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol (2014) 9.86

Autoimmunity correlates with tumor regression in patients with metastatic melanoma treated with anti-cytotoxic T-lymphocyte antigen-4. J Clin Oncol (2005) 9.72

Inflammation in prostate carcinogenesis. Nat Rev Cancer (2007) 9.08

Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer. N Engl J Med (2015) 8.80

Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer. J Clin Oncol (2008) 8.72

Inhibitory B7-family molecules in the tumour microenvironment. Nat Rev Immunol (2008) 8.17

A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med (2009) 7.45

Enterocolitis in patients with cancer after antibody blockade of cytotoxic T-lymphocyte-associated antigen 4. J Clin Oncol (2006) 7.40

Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity. Nat Med (2003) 7.35

Targeting the PD-1/B7-H1(PD-L1) pathway to activate anti-tumor immunity. Curr Opin Immunol (2012) 7.26

Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J Clin Oncol (2008) 6.23

Cancer immunotherapy comes of age. J Clin Oncol (2011) 5.87

Expression of programmed death 1 ligands by murine T cells and APC. J Immunol (2002) 5.78

Immunostimulatory monoclonal antibodies for cancer therapy. Nat Rev Cancer (2007) 5.65

Control of T(H)17/T(reg) balance by hypoxia-inducible factor 1. Cell (2011) 5.63

Tumor regression and autoimmunity in patients treated with cytotoxic T lymphocyte-associated antigen 4 blockade and interleukin 2: a phase I/II study. Ann Surg Oncol (2005) 5.36

Mechanisms of immune evasion by tumors. Adv Immunol (2006) 5.34

Gemcitabine plus bevacizumab compared with gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of the Cancer and Leukemia Group B (CALGB 80303). J Clin Oncol (2010) 5.21

Costimulatory B7-H1 in renal cell carcinoma patients: Indicator of tumor aggressiveness and potential therapeutic target. Proc Natl Acad Sci U S A (2004) 5.13

Phase III trial of bevacizumab plus interferon alfa versus interferon alfa monotherapy in patients with metastatic renal cell carcinoma: final results of CALGB 90206. J Clin Oncol (2010) 5.08

IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. J Exp Med (2009) 5.05

Blockade of B7-H1 and PD-1 by monoclonal antibodies potentiates cancer therapeutic immunity. Cancer Res (2005) 4.94

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 (2009) 4.68

B7-H1 determines accumulation and deletion of intrahepatic CD8(+) T lymphocytes. Immunity (2004) 4.60

Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A (2008) 4.43

Role of LAG-3 in regulatory T cells. Immunity (2004) 4.36

A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother (2002) 4.31

Cutting edge: An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity. J Immunol (2007) 4.29

Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol (2004) 4.25

Phase I study of the intravenous administration of attenuated Salmonella typhimurium to patients with metastatic melanoma. J Clin Oncol (2002) 4.15

B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res (2003) 3.96

Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res (2011) 3.81

B7-H4 expression identifies a novel suppressive macrophage population in human ovarian carcinoma. J Exp Med (2006) 3.75

Tumor progression can occur despite the induction of very high levels of self/tumor antigen-specific CD8+ T cells in patients with melanoma. J Immunol (2005) 3.73

Persistently activated Stat3 maintains constitutive NF-kappaB activity in tumors. Cancer Cell (2009) 3.71

Durable cancer regression off-treatment and effective reinduction therapy with an anti-PD-1 antibody. Clin Cancer Res (2012) 3.68

53BP1 is required for class switch recombination. J Cell Biol (2004) 3.57

PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol (2010) 3.51

Interferon-producing killer dendritic cells provide a link between innate and adaptive immunity. Nat Med (2006) 3.49

Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res (2013) 3.48

B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity (2003) 3.47

Randomized study of high-dose and low-dose interleukin-2 in patients with metastatic renal cancer. J Clin Oncol (2003) 3.38

Activity of sunitinib in patients with advanced neuroendocrine tumors. J Clin Oncol (2008) 3.34

Ipilimumab (anti-CTLA4 antibody) causes regression of metastatic renal cell cancer associated with enteritis and hypophysitis. J Immunother (2007) 3.32

Phase II study of erlotinib in patients with advanced biliary cancer. J Clin Oncol (2006) 3.31

B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance. Blood (2010) 3.21

Major histocompatibility complex class II-restricted presentation of a cytosolic antigen by autophagy. Eur J Immunol (2003) 3.12

Principles and use of anti-CTLA4 antibody in human cancer immunotherapy. Curr Opin Immunol (2006) 3.12

Combined immunotherapy with granulocyte-macrophage colony-stimulating factor-transduced allogeneic prostate cancer cells and ipilimumab in patients with metastatic castration-resistant prostate cancer: a phase 1 dose-escalation trial. Lancet Oncol (2012) 3.10

Phenotypic analysis of prostate-infiltrating lymphocytes reveals TH17 and Treg skewing. Clin Cancer Res (2008) 3.09

Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother (2010) 3.06