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Presenters: Dara L. Aisner and Gregory J. Riely

mutation is chemotherapy + anti–PD-1 (nivolumab) + CTLA-4 (ipilimumab) for 2 cycles. 21 A randomized study of 719 patients found that chemotherapy + 2 cycles of nivolumab/ipilimumab improved OS regardless of PD-L1 status: median OS was 14 versus 10

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Sharon H. Giordano, Anthony D. Elias, and William J. Gradishar

PARP, IDO, MEK, HDAC, and CTLA4. Immunologic agents are being evaluated in the adjuvant and neoadjuvant settings, including for their benefit in eradicating residual disease postoperatively. Promising Novel Approaches Many novel strategies are

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Jarushka Naidoo, Jiajia Zhang, Evan J. Lipson, Patrick M. Forde, Karthik Suresh, Kendall F. Moseley, Seema Mehta, Shawn G. Kwatra, Alyssa M. Parian, Amy K. Kim, John C. Probasco, Rosanne Rouf, Jennifer E. Thorne, Satish Shanbhag, Joanne Riemer, Ami A. Shah, Drew M. Pardoll, Clifton O. Bingham III, Julie R. Brahmer, and Laura C. Cappelli

immune checkpoint blockade . N Engl J Med 2018 ; 378 : 158 – 168 . 29320654 10.1056/NEJMra1703481 8. Gupta A , De Felice KM , Loftus EV Jr , . Systematic review: colitis associated with anti-CTLA-4 therapy . Aliment Pharmacol Ther 2015

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Presenter: Genevieve Boland

, hazard ratio; Ipi, ipilimumab; Nivo, nivolumab; NR, not reached; Pembro, pembrolizumab; RFS, relapse-free survival. In 2014, the CTLA-4 inhibitor ipilimumab became the first approved immunotherapy for the adjuvant treatment of melanoma, but its

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Presenters: Chad A. LaGrange, M. Dror Michaelson, and Colleen H. Tetzlaff

monotherapy, combination therapy with CTLA4/PD-1, or combination therapy with VEGFR TKI/PD-1. Two recent phase III trials of frontline treatment of RCC provide some guidance for treatment selection. 3 , 4 CheckMate 214 compared ipilimumab/nivolumab versus

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Tanya E. Keenan and Sara M. Tolaney

lymphocyte antigen-4 (CTLA-4) and PD-1, to improve the cytotoxicity and proliferative capacity of tumor-infiltrating lymphocytes (TILs). ICIs, including monoclonal antibodies against PD-1 (ie, pembrolizumab, nivolumab), PD-L1 (ie, atezolizumab, durvalumab

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Pooja Ghatalia and Elizabeth R. Plimack

studying nivolumab alone and in combination with the CTLA-4 inhibitor ipilimumab. The study included 3 cohorts with varying doses: nivolumab, 3 mg/kg (NIVO3) (n=78); nivolumab, 3 mg/kg + ipilimumab, 1 mg/kg (NIVO3+IPI1) (N=104); and nivolumab, 1 mg

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Matthew Zibelman and Elizabeth R. Plimack

metastatic melanoma using the combination of nivolumab with the cytotoxic T-lymphocyte–associated protein 4 (CTLA-4)–specific mAb ipilimumab. This combination demonstrated improved efficacy over both single agents, but with a consequent increase in grade 3

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Atish D. Choudhury and Philip W. Kantoff

to sipuleucel-T if also efficacious. Ipilimumab, a fully human monoclonal antibody targeting CTLA-4, a surface molecule that transduces inhibitory signals in T cells, is now being investigated in 2 randomized placebo-controlled phase III trials for

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David S. Ettinger, Douglas E. Wood, Wallace Akerley, Lyudmila A. Bazhenova, Hossein Borghaei, David Ross Camidge, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Thomas J. Dilling, M. Chris Dobelbower, Ramaswamy Govindan, Mark Hennon, Leora Horn, Thierry M. Jahan, Ritsuko Komaki, Rudy P. Lackner, Michael Lanuti, Rogerio Lilenbaum, Jules Lin, Billy W. Loo Jr., Renato Martins, Gregory A. Otterson, Jyoti D. Patel, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Steven E. Schild, Theresa A. Shapiro, Neelesh Sharma, James Stevenson, Scott J. Swanson, Kurt Tauer, Stephen C. Yang, Kristina Gregory, and Miranda Hughes

pathway are in clinical trials, notably atezolizumab and durvalumab, which target PD-L1. 15 – 17 In addition, clinical trials are ongoing in which PD-1/PD-L1 antibodies are combined with CTLA-4 antibodies. Although benefit from immune checkpoint