Unraveling Immunotherapy for Colorectal Cancer
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1 Unraveling Immunotherapy for Colorectal Cancer Todd S. Crocenzi, M.D. Providence Cancer Center/ Earle A. Chiles Research Institute Portland, OR 1
2 Disclosures Research Support: Bristol-Myers Squibb Research Support: Medimmune 2
3 Unraveling Immunotherapy for Colorectal Cancer: Key Points What is the evidence the immune system has prognostic importance in the management of colon cancer? What features of tumor immune suppression and tumor microenvironment are targets for immunooncology? How is proof of principle for immunotherapy in advanced colorectal cancer moving the field? 3
4 Colorectal Cancer: Global Problem Globocan
5 5
6 6
7 Immunoscore: Prognostic Biomarker in Resected Colon Cancer Galon J et al. J Clin Oncol 34, 2016 (suppl; abstr 3500) 7
8 Immunoscore: Prognostic Biomarker in Resected Colon Cancer Galon J et al. J Clin Oncol 34, 2016 (suppl; abstr 3500) 8
9 Immunoscore: Prognostic Biomarker in Resected Colon Cancer Galon J et al. J Clin Oncol 34, 2016 (suppl; abstr 3500) 9
10 Immunoscore: Prognostic Biomarker in Resected Colon Cancer Galon J et al. J Clin Oncol 34, 2016 (suppl; abstr 3500) 10
11 Cancer Immunoediting Schreiber RD et al. Science. 2011;331: Vesely MD et al. Annu Rev Immunol. 2011;29:
12 T cell / Antigen Presenting Cell Co-signaling Chen L et al. Nat Rev Immunol April ; 13(4):
13 The following are immune checkpoint inhibitor targets in clinical trials, except A. LAG3 B. OX40 C. KIR D. TIM3 13
14 The following are immune checkpoint inhibitor targets in clinical trials, except A. LAG3 B. OX40 C. KIR D. TIM3 14
15 Immunoediting: Elimination Equilibrium Escape Deepak M et al. Curr Opin Immunol Apr; 27:
16 Immunoediting: Elimination Equilibrium Escape Deepak M et al. Curr Opin Immunol Apr; 27:
17 Model for Boosting Tumor-Reactive Effector T Cells S Linch et al. Front Oncol
18 Prevalence of Somatic Mutations Across Human Cancer Types Alexandrov LB et al. Nature August 22; 500(7463):
19 PD-1 Blockade in Mismatch Repair Deficient Metastatic Colorectal Cancer Le DT et al. J Clin Oncol 33, 2015 (suppl; abstr LBA100). Le DT et al. N Engl J Med 2015; 372:
20 PD-1 Blockade in Mismatch Repair Deficient Metastatic Colorectal Cancer Le DT et al. J Clin Oncol 33, 2015 (suppl; abstr LBA100). Le DT et al. N Engl J Med 2015; 372:
21 PD-1 Blockade in Mismatch Repair Deficient Metastatic Colorectal Cancer Le DT et al. J Clin Oncol 33, 2015 (suppl; abstr LBA100). Le DT et al. N Engl J Med 2015; 372:
22 PD-1 Blockade in Mismatch Repair Deficient Metastatic Colorectal Cancer Le DT et al. J Clin Oncol 33, 2015 (suppl; abstr LBA100). Le DT et al. N Engl J Med 2015; 372:
23 PD-1 Blockade in Mismatch Repair Deficient Metastatic Colorectal Cancer Le DT et al. J Clin Oncol 33, 2015 (suppl; abstr LBA100). Le DT et al. N Engl J Med 2015; 372:
24 PD-1 Blockade in Mismatch Repair Deficient Metastatic Colorectal Cancer Le DT et al. J Clin Oncol 33, 2015 (suppl; abstr LBA100). Le DT et al. N Engl J Med 2015; 372:
25 PD-1 Blockade in Mismatch Repair Deficient Metastatic Colorectal Cancer Le DT et al. J Clin Oncol 33, 2015 (suppl; abstr LBA100). Le DT et al. N Engl J Med 2015; 372:
26 PD-1 Blockade in Mismatch Repair Deficient Metastatic Colorectal Cancer Le DT et al. J Clin Oncol 33, 2015 (suppl; abstr LBA100). Le DT et al. N Engl J Med 2015; 372:
27 43 yo F metastatic colon adenocarcinoma. RAS-mutant/ MMRdeficient. Refractory to SOC therapy. Pembrolizumab C1D1=3/30/15. Pre- pembrolizumab Mar 2015 On pembrolizumab Jun 2015 On pembrolizumab Sep
28 Immunotherapy for Colorectal Cancer: After the Pembro study Marked tumor responses are possible (? Complete responses) in tumors traditionally viewed as "non-immunogenic" Sustained responses occur implying anti-tumor immune memory is achievable Prolonged survivals in treatment-refractory patients implies a survival advantage; however, RCT data still lacking 28
29 29
30 Combination Ipilimumab + Nivolumab: Single dose in metastatic melanoma Chapman PB et al. N Engl J Med 2015;372:
31 Immune Checkpoint Inhibitors: Toxicity 31
32 What is the treatment of choice for management of grade 3-4 immunerelated hepatitis not responsive to highdose steroids? A. ursodiol B. IVIG C. Infliximab D. Mycophenolate mofetil 32
33 What is the treatment of choice for management of grade 3-4 immunerelated hepatitis not responsive to highdose steroids? A. ursodiol B. IVIG C. Infliximab D. Mycophenolate mofetil 33
34 62 yo M metastatic colon adenocarcinoma. RAS-wt/ MMR-proficient. Refractory to SOC therapy. Nivolumab + varlilumab C1D1=5/15/15. Pre- Rx baseline Apr 2015 On nivolumab + varlilumab Jun 2015 On nivolumab + varlilumab Sep
35 Combination PD-L1 and MEK Inhibition: atezolizumab + cobimetinib Bendell JC et al. J Clin Oncol 34, 2016 (suppl; abstr 3502). 35
36 Combination PD-L1 and MEK Inhibition Bendell JC et al. J Clin Oncol 34, 2016 (suppl; abstr 3502). 36
37 Combination PD-L1 and MEK Inhibition Bendell JC et al. J Clin Oncol 34, 2016 (suppl; abstr 3502). 37
38 Combination OX40 Agonist + PD-L1 Inhibitor 38
39 PO1 Grant Submission: Combination Chemotherapy + Immunotherapy 39
40 P01 Grant: Immunoprofiling and Immunotherapy in Colon Cancer Project 1 Prospective clinical trial, with companion immunotherapy trial Prognostic utility of immunoprofiling to stage CC patients & predict responses Core A Administration & Multicenter Trial Operations Center Organization and Data Project 2 Microbiome & metabolomics The interplay between host/tumor immune response and the microbiome Project 3 Molecular aspects of immunoscore, immunoprofile, & immunotherapy response The role of host anti-tumor immunity in therapeutic efficacy Core B Biostatistics Data and Analysis Core C Molecular & Immunological Monitoring RNA-Seq & immune profiling data Core D Microbiome/Metabolomics 16S & metabolomics data Immunoprofiling and Immunotherapy in Colon Cancer 40 40
41 Microbiome and Colorectal Cancer Gagniere J et al. World J Gastroenterol Jan 14; 22(2):
42 Microbiome and Colorectal Cancer Gagniere J et al. World J Gastroenterol Jan 14; 22(2):
43 Unraveling Immunotherapy for Colorectal Cancer John Hopkins University/ Sidney Kimmel Comprehensive Cancer Center Dung Le, M.D. Luiz Diaz, Jr, M.D. John Wayne Cancer Institute Anton Bilchik, M.D. Swedish Cancer Institute Philip Gold, M.D. Providence Cancer Center/ GI Cancer Research Program and Phase 1 Program Yue-yun To, R.N. Anthonette Guy, R.N. Tara Foote, R.N. Kim Sutcliffe, R.N. Kate Tripp, R.N. Mark Whiteford, M.D. Providence Cancer Center/ Earle A. Chiles Research Institute Bernard Fox, Ph.D. Carlo Bifulco, M.D. Marka Crittenden, M.D., Ph.D. Kristina Young, M.D., Ph.D. Walter Urba, M.D., Ph.D. 43
44 Unraveling Immunotherapy for Colorectal Cancer: Key Points What is the evidence the immune system has prognostic importance in the management of colon cancer? What features of tumor immune suppression and tumor microenvironment are targets for immunooncology? How is proof of principle for immunotherapy in advanced colorectal cancer moving the field? 44
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