＜Immuno-Oncology in Lung Cancer＞
Giuseppe Giaccone MD.
・Johnson et al, ASCO 2013, NSCLC and genetic mutation
・PD-1 inhibitors: Nivolumab, Pembrolizumab, etc.
・PD-L1 inhibitors: Atezorizumab, Durvalumab, avelumab, etc.
・Tumor immunology overview
Padmanee Sharma, James P. Allison, Science 56-61, 2015
Freeman, Sharpe, Nature Immunology 2012
・Nivolumab phase I: Gettinger J Clin Oncol 2004-1012, 2015
129 NSCLC patients enrolled→15% durable response observed ( survival curve seems to be plateau )
ORR 30% ( patients of >5 pack-year smoker )
0% ( light smoker or never smoker )
3 patients died due to ILD ( 2% )
endocrinopathy
・CheckMate 017 study, Brahmer et al, N Engl J Med 123-135, 2015
for Sq patients, PD-L1 expression tested with DACO 28-8 antibody
・CheckMate 057 study, Borghaei et al, N Engl J Med 1627-1639, 2015
for non-Sq patients, PD-L1 expression tested with DACO 28-8 antibody
survival curve crossing as IPASS study
duration of response: 17.2M vs 5.6M
・KEYNOTE 001 study, phase I, Garon et al, N Engl J Med 2018-2028, 2015
n=495 ( 1143 screened )
PD-L1 expression membranous staining tested with 22C3 PharmaDx Test
・KEYNOTE 010 study, phase III, for NSCLC, Herbst et al, Lancet Oncol 2015
・CheckMate 026: 1st line Nivolumab vs platinum doublet, primary endpoint:PFS ( unfortunately! )
・Atezolizumab ( MPDL3280A ): anti-PD-L1 antibody
phase I: PCD4989g study, Nature Nov 27, 2014
phase II: POPLAR study, Spira et al, ASCO 2015
・Durvalumab ( MEDI 4736 ): anti PD-L1 antibody
Rizvi et al, ASCO 2015 ( TATTON trial )
・Avelumab: anti PD-L1 antibody
JAVELIN trial for solid tumor, Gulley et al, ASCO 2015
・Alexandrov et al, Science 2013: mutation burden
Naiger, Rizvi et al, Science 123-128, 2015
・CheckMate 012 study: Nivolumab + Chemotherapy
・KEYNOTE 021 study: Pemblorizumab +Chemotherapy
・ICIs combination
Mellman et al, Nature 2011
Rizvi et al, WCLC 2015
CheckMate 022
・ILD frequency
CheckMate 017: 5%
CheckMate 057: 3%
CheckMate 063: 5%
KEYNOTE 001: 4.8%
・irAE ( immune-related Adverse Event )
skin, endocrinopathy, colitis, etc.
