Evolving Paradigms in Immuno-Oncology: References

Evolving Paradigms, Immuno-Oncology: Checkpoint Inhibitors, Volume 1, Issue 1

This feature covers the "Treatment Strategies and Clinical Evidence for Checkpoint Inhibiton" section of the current Evolving Paradigms in Immuno-Oncology issue.


  1. Swann JB, Smyth MJ. Immune surveillance of tumors. J Clin Invest. 2007;117(5):1137-1146.
  2. Curiel TJ. Cancer immunotherapy paradigms, practice and promise. New York, NY: Springer Publishing Co; 2013.
  3. McCarthy EF. The toxins of William B. Coley and the treatment of bone and soft-tissue sarcomas. Iowa Orthop J. 2006;26:154-158.
  4. Coley WB. The treatment of inoperable sarcoma with the mixed toxins of erysipelas and bacillus prodigiosus: immediate and final results in one hundred and forty cases. JAMA. 1898;XXXI(9):456-465.
  5. Higgins GK, Pack GT. The effects of virus therapy on the microscopic structure of human melanomas. Am J Pathol. 1951;27(4):728-729.
  6. Morton DL, Eilber FR, Joseph WL, Wood WC, Trahan E, Ketcham AS. Immunological factors in human sarcomas and melanomas: a rational basis for immunotherapy. Ann Surg. 1970;172(4):740-749.
  7. TICE Bacillus Calmette-Guérin (BCG) LIVE For intravesical use. [Prescribing Information]. Durham, NC: Organon Teknika Corp, LLC; February 2009.
  8. Berman D, Korman A, Peck R, Feltquate D, Lonberg N, Canetta R. The development of immunomodulatory monoclonal antibodies as a new therapeutic modality for cancer: the Bristol-Myers Squibb experience. Pharmacol Ther. 2015;148:132-153.
  9. Falkson CI, Falkson G, Falkson HC. Improved results with the addition of interferon alfa-2b to dacarbazine in the treatment of patients with metastatic malignant melanoma. J Clin Oncol. 1991;9(8):1403-1408.
  10. Proleukin (aldesleukin) for injection [prescribing information]. San Diego, CA: Prometheus Laboratories Inc; January 2015.
  11. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17(7):2105-2116.
  12. Chambers CA, Kuhns MS, Egen JG, Allison JP. CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annu Rev Immunol. 2001;19:565-594.
  13. Zhang Y, Huang S, Gong D, Qin Y, Shen Q. Programmed death-1 upregulation is correlated with dysfunction of tumor-infiltrating CD8+ T lymphocytes in human non-small cell lung cancer. Cell Mol Immunol. 2010;7(5):389-395.
  14. Camacho LH. CTLA-4 blockade with ipilimumab: biology, safety, efficacy, and future considerations. Cancer Med. 2015;4(5):661-672.
  15. Linsley PS, Brady W, Urnes M, Grosmaire LS, Damle NK, Ledbetter JA. CTLA-4 is a second receptor for the B cell activation antigen B7. J Exp Med. 1991;174(3):561-569.
  16. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9-29.
  17. Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711-723.
  18. Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science. 2013;342(6165):1432-1433.
  19. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12(4):252-264.
  20. Okazaki T, Iwai Y, Honjo T. New regulatory co-receptors: inducible co-stimulator and PD-1. Curr Opin Immunol. 2002;14(6):779-782.
  21. Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002;8(8):793-800.
  22. Chow L. Exploring Novel Immune-Related Toxicities and Endpoints with Immune-Checkpoint Inhibitors in Non-Small Cell Lung Cancer. ASCO Educational Book. 2013:7.
  23. Keytruda (pembrolizumab) injection [package insert]. Whitehouse Station, NJ: Merck; November 2015.
  24. Opdivo (nivolumab) injection [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; November 2015.
  25. Wang C, Thudium KB, Han M, et al. In vitro characterization of the anti—PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res. 2014;2(9):846-856.
  26. Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015;372(21):2018-2028.
  27. Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N. 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;99(19):12293-12297.
  28. Butte MJ, Keir ME, Phamduy TB, Sharpe AH, Freeman GJ. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity. 2007;27(1):111-122.
  29. Sznol M, Chen L. Antagonist antibodies to PD-1 and B7-H1 (PD-L1) in the treatment of advanced human cancer. Clin Cancer Res. 2013;19(5):1021-1034.
  30. Kondo A, Yamashita T, Tamura H, et al. Interferon-gamma and tumor necrosis factor- alpha induce an immunoinhibitory molecule, B7-H1, via nuclear factor-kappaB activation in blasts in myelodysplastic syndromes. Blood. 2010;116(7):1124-1131.
  31. Ibrahim R, Stewart R, Shalabi A. PD-L1 blockade for cancer treatment: MEDI4736. Semin Oncol. 2015;42(3):474-483.
  32. Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563-567.
  33. Keir ME, Butte MJ, Freeman GJ, Sharpe AH. PD-1 and its ligands in tolerance and immunity. Annu Rev Immunol. 2008;26:677-704.
  34. Wolchok JD, Hoos A, O’Day S, et al. Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clin Cancer Res. 2009;15(23):7412-7420.
  35. Nishino M, Gargano M, Suda M, Ramaiya NH, Hodi FS. Optimizing immune-related tumor response assessment: does reducing the number of lesions impact response assessment in melanoma patients treated with ipilimumab? J Immunother Cancer. 2014;2:17.
  36. Naidoo J, Page DB, Li BT, et al. Toxicities of the anti—PD-1 and anti-PD-L1 immune checkpoint antibodies. Ann Oncol. 2015;26(12):2375-2391.
  37. Larkin J, Chiarion-Sileni V, Gonzalez R, et al. Combined nivolumab and ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(1):23-34.
  38. Puzanov I. Efficacy based on tumor PD-L1 expression in Keynote-002, a randomized com- parison of pembrolizumab (MK-3475) versus chemotherapy in patients with ipilimumab-refractory advanced melanoma. American Society of Clinical Oncology. Annual Meeting. Chicago, IL. J Clin Oncol. 2015;33(suppl; abstr 3012).
  39. Dong H. A novel method for identifying downstream signals in tumor-reactive T cells folowing PD-1 engagement and monitering engodenous tumor immunity and immunotherapy. J Clin Oncol. 32:5s, 2014 (suppl; abstr 3049).
  40. Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515(7528):558-562.
  41. Roszik J. A novel algorithm applicable to cancer next-generation sequencing panels to predict total tumor mutation load and correlation with clinical outcomes in melanoma. J Clin Oncol. 2015;33(suppl; abstr 9071).
  42. Joseph RW. Model-bases analysis of the relationshiop between pembrolizumab (MK-3475) exposure and efficacy in patients with advanced or metastatic melanoma. J Clin Oncol. 2015;33(suppl; abstr 3068).
  43. Joseph RW, Elassaiss-Schaap J, Wolchok JD, et al. Baseline tumor size as an independent prognostic factor for overall survival in patients with metastatic melanoma treated with the anti—PD-1 monoclonal antibody MK-3475. J Clin Oncol. 32:5s, 2014 (suppl; abstr 3015).
  44. Johnson DB, Lovly CM, Flavin M, et al. Impact of NRAS mutations for patients with advanced melanoma treated with immune therapies. Cancer Immunol Res. 2015;3(3):288-295.
  45. Blank C. Serum lactade dehydrogenase (LDH) as a prognostic selection criterion for ipilimumab treatment in metastatic melanoma. J Clin Oncol. 31, 2013 (suppl; abstr 3036).
  46. Berman DM, Wolchok J, Weber J, Hamid O, O’Day S, Chasalow SD. Association of peripheral blood absolute lymphocyte count (ALC) and clinical activity in patients (pts) with advanced melanoma treated with ipilimumab. J Clin Oncol. 27:15s, 2009 (suppl; abstr 3020).
  47. Ku GY, Yuan J, Page DB, et al. Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival. Cancer. 2010;116(7):1767-1775.
  48. Rigel DS. Epidemiology of melanoma. Semin Cutan Med Surg. 2010;29(4):204-209.
  49. Guy GP, Jr., Thomas CC, Thompson T, et al. Vital signs: melanoma incidence and mortality trends and projections - United States, 1982-2030. MMWR Morb Mortal Wkly Rep. 2015;64(21):591-596.
  50. Cancer Fact Sheet No 297. 2015; http://www.who.int/mediacentre/factsheets/fs297/en/. Accessed May 27, 2015.
  51. National Cancer Institute. Surveillance, Epidemiology, and End Results Program stat fact sheets: Melanoma of the skin. http://seer.cancer.gov/statfacts/html/melan.html. Accessed November 20, 2015.
  52. Lucas RM, McMichael AJ, Armstrong BK, Smith WT. Estimating the global disease burden due to ultraviolet radiation exposure. Int J Epidemiol. 2008;37(3):654-667.
  53. Uong A, Zon LI. Melanocytes in development and cancer. J Cell Physiol. 2010;222(1):38-41.
  54. BRAF B-Raf proto-oncogene, serine/threonine kinase [Homo sapiens (human)]. Updated: November 12, 2015; http://www.ncbi.nlm.nih.gov/gene/673. Accessed November 17, 2015.
  55. NRAS neuroblastoma RAS viral (v-ras) oncogene homolog [Homo sapiens(human)]. Updated: November 8, 2015; http://www.ncbi.nlm.nih.gov/gene/4893. Accessed November 17, 2015.
  56. National Comprehensive Cancer Network Clinical Practice Guidelines Melanoma. Version 1.2016. http://www.nccn.org/professionals/physician_gls/PDF/melanoma.pdf. Accessed November 22, 2015.
  57. Eggermont AM, Chiarion-Sileni V, Grob JJ, et al. Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomised, double-blind, phase III trial. Lancet Oncol. 2015;16(5):522-530.
  58. Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dosecomparison cohort of a phase I trial. Lancet. 2014;384(9948):1109-1117.
  59. Weber JS, D’Angelo SP, Minor D, et al. Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti—CTLA-4 treatment (CheckMate 037): a randomised, controlled, open-label, phase III trial. Lancet Oncol. 2015;16(4):375-384.
  60. Yervoy (ipilimumab) injection [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; November 2015.
  61. Postow MA, Chesney J, Pavlick AC, et al. Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015;372(21):2006-2017.
  62. NCT01927419. Phase II, randomized, double blinded, study of nivolumab (BMS-936558) in combination with ipilimumab vs ipilimumab alone in subjects with previously un- treated, unresectable or metastatic melanoma (CheckMate 069). https://clinicaltrials. gov/ct2/show/NCT01927419. Accessed November 23, 2015.
  63. NCT02027961. A phase I open-label study of safety and tolerability of MEDI4736 in subjects with metastatic or unresectable melanoma in combination with dabrafenib and trametinib or with trametinib alone. November 2, 2015; https://clinicaltrials.gov/ct2/ show/NCT02027961. Accessed November 17, 2015.
  64. Ribas A, Butler M, Lutzky J, et al. Phase I study combining anti-PD-L1 (MEDI4736) with BRAF (dabrafenib) and/or MEK (trametinib) inhibitors in advanced melanoma [ASCO abstract 3003]. J Clin Oncol 33, 2015 (suppl; abstr 3003).
  65. Lung Cancer (Non-Small Cell). American Cancer Society website. October 2, 2015; http:// www.cancer.org/acs/groups/cid/documents/webcontent/003115-pdf.pdf. Accessed November 15, 2015.
  66. National Cancer Institute. Surveillance, Epidemiology, and End Result Program stat fact sheet: lung and bronchus cancer http://seer.cancer.gov/statfacts/html/lungb.html. Accessed November 19, 2015.
  67. Homet Moreno B, Ribas A. Anti-programmed cell death protein-1/ligand-1 therapy in different cancers. Br J Cancer. 2015;112(9):1421-1427.
  68. Stinchcombe TE. Unmet needs in squamous cell carcinoma of the lung: potential role for immunotherapy. Med Oncol. 2014;31(5):960.
  69. National Comprehensive Cancer Network Clinical Practice Guidelines Non-small cell lung cancer. Version 1.2016. http://www.nccn.org/professionals/physician_gls/pdf/nscl. pdf. Accessed November 19, 2015.
  70. Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squa- mous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373(2):123-135.
  71. Borghaei H, Paz-Ares L, Horn L, et al. Nivolumab versus Docetaxel in Advanced Nonsqua- mous Non-Small-Cell Lung Cancer. N Engl J Med. 2015;373(17):1627-1639.
  72. NCT02259621. Neoadjuvant anti—PD-1, nivolumab in resectable NSCLC (NA_00092076). ClinicalTrials.gov. October 2015; https://clinicaltrials.gov/ct2/show/NCT02259621. Accessed November 13, 2015.
  73. NCT02179671. Immune-modulated study of selected small molecules (gefitinib, AZD9291, or selumetinib + cocetaxel) or a 1st immune-mediated therapy (IMT; treme- limumab) with a sequential switch to a 2nd IMT (MEDI4736) in patients with locally advanced or metastatic non-small-cell lung cancer. https://clinicaltrials.gov/ct2/show/ NCT02179671. Accessed November 23, 2015.
  74. NCT02125461. A global study to assess the effects of MEDI4736 following concurrent chemoradiation in patients with stage III unresectable non-small cell lung cancer (PA- CIFIC). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT02125461?term=NCT0 2125461&rank=1. Accessed November 15, 2015.
  75. NCT02352948. A global study to assess the effects of MEDI4736, given as monotherapy or in combination with tremelimumab determined by PD-L1 expression versus standard of care in patients with locally advanced or metastatic non small cell lung cancer (ARC- TIC). https://clinicaltrials.gov/ct2/show/NCT02352948?term=NCT02352948&rank=1. Accessed November 12, 2015.
  76. NCT02453282. Phase III open label first line therapy study of MEDI 4736 with or with- out tremelimumab versus SOC in non small-cell lung cancer (NSCLC). (MYSTIC). https:// clinicaltrials.gov/ct2/show/NCT02453282. Accessed November 19, 2015.
  77. Rizvi N. Phase III, randomized, open-label study of durvalumab (MEDI4736) in combina- tion with tremelimumab or durvalumab alone versus platinum-based chemotherapy in first-line treatment of patients with advanced/metastatic NSCLC: MYSTIC. J Immunother Cancer. 2015, 3(Suppl 2):P171.
  78. NCT02542293. Study of 1st line therapy study of MEDI4736 with tremelimumab versus SoC in non small-cell lung cancer (NSCLC) (NEPTUNE). https://clinicaltrials.gov/ct2/ show/NCT02542293. Accessed November 23, 2015.
  79. NCT02273375. Double blind placebo controlled study of adjuvant MEDI4736 in com- pletely resected NSCLC. https://clinicaltrials.gov/ct2/show/NCT02273375. Accessed November 23, 2015.
  80. NCT02154490. Lung-MAP: S1400 biomarker-targeted second-line therapy in treating patients with recurrent stage IIIB-IV squamous cell lung cancer. https://clinicaltrials.gov/ ct2/show/NCT02154490. Accessed November 23, 2015.
  81. NCT02087423. A global study to assess the effects of MEDI4736 in patients with locally advanced or metastatic non small cell lung cancer (ATLANTIC). https://clinicaltrials.gov/ ct2/show/NCT02087423. Accessed November 12, 2015.
  82. U.S. FDA grants breakthrough therapy designation for Roche’s investigational cancer immunotherapy MPDL3280A (anti-PDL1) in non-small cell lung cancer [Press Release]. Basel, Switzerland: Roche Group Media Relations; February 2, 2015. http://www.roche. com/med-cor-2015-02-02-e.pdf. Accessed November 14, 2015.
  83. Spira AI, Park K, Mazières J, et al. Efficacy, safety and predictive biomarker results from a randomized phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POP- LAR) [ASCO abstract 8010]. J Clin Oncol. 33, 2015 (suppl; abstr 8010).
  84. NCT02031458. A phase II study of MPDL3280A (an engineered anti-PDL1 antibody) in patients with PD-L1 positive locally advanced or metastatic non-small cell lung cancer - “BIRCH”. https://clinicaltrials.gov/ct2/show/NCT02031458. Accessed November 19, 2015.
  85. NCT02008227. A randomized phase III study of MPDL3280A (an engineered anti-PDL1 antibody) compared with docetaxel in patients with locally advanced or metastatic non- small cell lung cancer who have failed platinum therapy - “OAK”. https://clinicaltrials. gov/ct2/show/NCT02008227. Accessed November 19, 2015.
  86. NCT02409355. A study of MPDL3280A compared with gemcitabine + cisplatin or car- boplatin in patients with stage IV squamous non-small cell lung cancer [IMpower 111]. https://clinicaltrials.gov/ct2/show/NCT02409355. Accessed November 19, 2015.
  87. NCT02367794. A phase III study of MPDL3280A (anti-PD-L1) in combination with carbo- platin + paclitaxel or carboplatin + nab-paclitaxel compared with carboplatin + nab-paclitaxel in patients with stage IV squamous non-small cell(NSCLC) [IMpower131].https://clinicaltrials.gov/ct2/show/NCT02367794. Accessed November 19, 2015.
  88. NCT01903993. A randomized phase II study of MPDL3280A (an engineered anti-PDL1 antibody) compared with docetaxel in participants with locally advanced or metastatic non-small cell lung cancer who have failed platinum therapy - “POPLAR”. https://clinical- trials.gov/ct2/show/NCT01903993. Accessed November 24, 2015.
  89. NCT02395172. Avelumab in non-small cell lung cancer (JAVELIN Lung 200). https:// clinicaltrials.gov/ct2/show/NCT02395172. Accessed November 25, 2015.
  90. Rizvi NA, Mazieres J, Planchard D, et al. Activity and safety of nivolumab, an anti—PD- 1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase II, single-arm trial. Lancet Oncol. 2015;16(3):257-265.
  91. NCT02054806. Study of pembrolizumab (MK-3475) in participants with advanced solid tumors (MK-3475-028/KEYNOTE-28). https://clinicaltrials.gov/show/NCT02054806. Accessed November 19, 2015.
  92. NCT01928394. A Phase I/2, open-label study of nivolumab monotherapy or nivolumab combined with ipilimumab in subjects with advanced or metastatic solid tumors. https:// clinicaltrials.gov/show/NCT1928394. Accessed November 18, 2015.
  93. Antonia SJ, Bendell JC, Taylor MH, et al. Phase I/II study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC): CA209-032. J Clin Oncol 33, 2015 (suppl; abstr 7503).
  94. National Cancer Institute. Surveillance, Epidemiology, and End Results Program stat fact sheets: bladder cancer. http://seer.cancer.gov/statfacts/html/urinb.html. Accessed November 19, 2015.
  95. American Cancer Society website. Bladder cancer. http://www.cancer.org/acs/groups/ cid/documents/webcontent/003085-pdf.pdf. Accessed November 24, 2015.
  96. Fuge O, Vasdev N, Allchorne P, Green JS. Immunotherapy for bladder cancer. Res Rep Urol. 2015;7:65-79.
  97. Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol. 1976;116(2):180-183.
  98. National Comprehensive Cancer Network Clinical Practice Guidelines Non-small cell lung cancer. Version 2.2015. . http://www.nccn.org/professionals/physician_gls/pdf/ bladder.pdf. Accessed November 25, 2015.
  99. Petrylak DP, Powles T, Bellmunt J, et al. A phase Ia study of MPDL3280A (anti-PDL1): Updated response and survival data in urothelial bladder cancer (UBC) . J Clin Oncol.33, 2015 (suppl; abstr 4501).
  100. Liakou CI, Kamat A, Tang DN, et al. CTLA-4 blockade increases IFNgamma-producing CD4+ICOShi cells to shift the ratio of effector to regulatory T cells in cancer patients. Proc Natl Acad Sci U S A. 2008;105(39):14987-14992.
  101. Carthon BC, Wolchok JD, Yuan J, et al. Preoperative CTLA-4 blockade: tolerability and immune monitoring in the setting of a presurgical clinical trial. Clin Cancer Res. 2010;16(10):2861-2871.
  102. Bellmunt J, Sonpavde G, De Wit R, et al. KEYNOTE-045: Randomized phase III trial of pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for previously treated metastatic urothelial cancer. J Clin Oncol 33, 2015 (suppl; abstr TPS4571).
  103. Bajorin DF, Plimack ER, Siefker-Radtke AO, et al. KEYNOTE-052: Phase II study of pembrolizumab (MK-3475) as first-line therapy for patients (pts) with unresectable or metastatic urothelial cancer ineligible for cisplatin-based therapy. J Clin Oncol 33, 2015 (suppl; abstr TPS4572).
  104. Motzer RJ, Rini BI, McDermott DF, et al. Nivolumab for metastatic renal cell carcinoma: results of a randomized phase II trial. J Clin Oncol. 2015;33(13):1430-1437.
  105. Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in Aadvanced renal-cell carcinoma. N Engl J Med. 2015;373(19):1803-1813.
  106. NCT02105636. Trial of nivolumab vs therapy of investigator’s choice in recurrent or metastatic head and neck carcinoma (CheckMate 141). https://clinicaltrials.gov/ct2/ show/NCT02105636. Accessed November 25, 2015.
  107. Cohen EW, Machiels JPH, Harrington KJ, et al. KEYNOTE-040: A phase III randomized trial of pembrolizumab (MK-3475) versus standard treatment in patients with recurrent or metastatic head and neck cancer. J Clin Oncol. 33, 2015 (suppl; abstr TPS6084).
  108. NCT02358031. A study of pembrolizumab (MK-3475) for first line treatment of recurrent or metastatic squamous cell cancer of the head and neck (MK-3475-048/KEYNOTE-048). https://clinicaltrials.gov/ct2/show/NCT02358031. Accessed November 25, 2015.
  109. NCT02207530. Phase II study of MEDI4736 monotherapy in treatment of recurrent or metastatic squamous cell carcinoma of the head and neck. https://clinicaltrials.gov/ct2/show/NCT02207530. Accessed November 23, 2015.
  110. NCT02319044. Phase II study of MEDI4736, tremelimumab, and MEDI4736 in combination w/ tremelimumab squamous cell carcinoma of the head and neck. https://clinicaltrials.gov/ct2/show/NCT02319044. Accessed November 23, 2015.
  111. NCT02499328. Study to assess combination of MEDI4736 with either AZD9150 or AZD5069 in patients with metastatic squamous cell carcinoma of head and neck. https://clinicaltrials.gov/ct2/show/NCT02499328. Accessed November 23, 2015.
  112. NCT02369874. Study of MEDI4736 monotherapy and in combination with tremelim- umab versus standard of care therapy in patients with head and neck cancer. https://clinicaltrials.gov/ct2/show/NCT02369874. Accessed November 23, 2015.
  113. NCT02155647. Avelumab in subjects with Merkel cell carcinoma (JAVELIN Merkel 200). https://clinicaltrials.gov/ct2/show/NCT02155647. Accessed November 25, 2015.
  114. Tremelimumab granted orphan drug designation by US FDA for treatment of malignant mesothelioma [press release]. April 15, 2015. https://www.astrazeneca.com/our-compa- ny/media-centre/press-releases/2015/tremelimumab-orphan-drug-designation-us-fda-malignant-mesothelioma-treatment-15042015.html. Accessed November 12, 2015.
  115. NCT01843374. Randomized, double-blind study comparing tremelimumab to placebo in subjects with unresectable malignant mesothelioma. https://clinicaltrials.gov/ct2/show/ NCT01843374. Accessed November 25, 2015.
  116. NCT02530125. Pidilizumab in treating patients with stage III-IV diffuse large B-Cell lymphoma following first remission. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/ show/NCT02530125. Accessed November 15, 2015.
  117. NCT02118337. A phase I, open-label study to evaluate the safety and tolerability of MEDI0680 (AMP-514) in combination with MEDI4736 in subjects with advanced malig- nancies. https://clinicaltrials.gov/ct2/show/NCT02118337. Accessed November 25, 2015.
  118. NCT02335424. Study of pembrolizumab (MK-3475) in participants with advanced urothelial cancer (MK-3475-052/KEYNOTE-52). https://clinicaltrials.gov/ct2/show/ NCT02335424. Accessed December 1, 2015.
  119. NCT02256436. A study of pembrolizumab (MK-3475) versus paclitaxel, docetaxel, or vinflunine for participants with advanced urothelial cancer (MK-3475-045/KEYNOTE-045). https://clinicaltrials.gov/ct2/show/NCT02256436. Accessed November 25, 2015.
  120. NCT01354431. BMS-936558 (MDX-1106) In subjects with advanced/metastatic clear-cell renal cell carcinoma (RCC). https://clinicaltrials.gov/ct2/show/NCT01354431. Accessed December 1, 2015.
  121. NCT01524991. First-line gemcitabine, cisplatin + ipilimumab for metastatic urothelial carci- noma. https://clinicaltrials.gov/ct2/show/NCT01524991. Accessed November 25, 2015.