where are we with check-point inhibitors in gastric cancer? · orr and waterfall in keynote-059...
TRANSCRIPT
Kei Muro, [email protected]
Department of Clinical OncologyAichi Cancer Center Hospital
Nagoya, JAPAN
Where Are We with Check-Point Inhibitors in Gastric Cancer?
21 June 2018, Barcelona
Session VII: Metastatic Gastric Cancer
Disclosure
Research Funding: Gilead Sciences, Merck Serono, MSD, Daiichi Sankyo, Sanofi, Ono, Shionogi, Medisience Planning, Pfizer, and Kyowa Hakko Kirin
Lecture Fee:Chugai, Eli Lilly, Takeda, Ono, Taiho, and Bayer
Kei Muro, MD.
Hayakawa Y, et al. Nature Reviews Cancer 16: 305-318, 2016
Molecular Subtypes of Gastric Cancer
T cell activation OFF
Suppression of T cell activation by PD-1/PD-L1(or PD-L2) interaction3)
Escape from immune surveillance3) Tumor cell
inactivated T cell
Attack against tumor cells
OFF
tumor cell inactivated T cellPD-L2
PD-L1
PD-1
antigen-presenting cell(dendritic cells etc.)
1) Chen DS et al. Immunity 39: 1-10, 20132) Mellman I et al. Nature 480: 480-489, 2011
3) Pardoll DM. Nat Rev Cancer 12: 252-264, 2012
antigen presentation1,2)
naïve T cell
Lymph node
tumor-specific antigen
Migration and infiltration of T cells into tumors2)
Editorial supervision: Division of Cellular Signaling Institute for Advanced Medical Research, Keio University School of Medicine, Prof. Yutaka Kawakami
Escape from Immune Surveillance
T cellsactiva
tion OFF
Suppression of T cell activation by PD-1/PD-L1(or PD-L2) interaction 2,3)
Anti-PD-1 therapy
PD-L2PD-L1tumor cell
PD-1
activated T cell
PD-L2
PD-L1
PD-1
Anti-PD-1 Therapy
Killing of tumor cells by reactivation of T cells5) Tumor cell
inactivated T cell
Attack against tumor cells
antigen-presenting cell(dendritic cells etc.)
antigen presentation 1,2)
naïve T cell
reactivation of T cells by suppression of PD-1/PD-L1(or PD-L2) interaction3,4)
Lymph node
tumor-specific antigen
Editorial supervision: Division of Cellular Signaling Institute for Advanced Medical Research, Keio University School of Medicine, Prof. Yutaka Kawakami
Cancel of Immunity Suppressionby Anti PD-1 Therapy
1) Chen DS et al. Immunity 39: 1-10, 2013; 2) Mellman I et al. Nature 480: 480-489, 20113) Pardoll DM. Nat Rev Cancer 12: 252-264, 2012; 4) Postow MA et al. J Clin Oncol 33: 1974-1982, 2015
5) Topalian SL et al. Curr Opin Immunol 24: 207-212, 2012
Line Study Agent Tested Targeting Control Arm Primary EP
1st ToGA (HER2) trastuzumab HER2 XP/FP OS
LOGiC(HER2) lapatinib HER2 XELOX OS
JACOB (HER2) pertuzumab HER2 XP + trastuzumab OS
AVAGAST bevacizumab VEGF XP OS
AVATAR bevacizumab VEGF XP OS
EXPAND cetuximab EGFR XP PFS
REAL-3 panitumumab EGFR EOX OS
RILOMET-1, 2 rilotumumab MET ECX, XP OS
METGastric onartuzumab MET mFOLFOX6 OS
RAINFALL ramucirumab VEGFR2 XP PFS (OS)
KEYNOTE 062 pembrolizumab PD-1 XP/FP PFS, OS
ATTRACTION-04 nivolumab PD-1 SOX/CapeOX PFS, OS
CheckMate-649 nivolumab,nivo+ipilimumab PD-1 FOLFOX/CapeOX OS in PD-L1+
GS-5745 (Gilead) andecaliximab MMP9 mFOLFOX6 OS
1st maintenance JAVELIN GASTRIC 100 avelumab PD-L1 FOLFOX/CapeOX PFS, OS
2nd TyTAN (HER2) lapatinib HER2 weekly paclitaxel OS
GATSBY (HER2) TDM-1 HER2 weekly paclitaxel OS
RAINBOW ramucirumab VEGFR2 weekly paclitaxel OS
REGARD everolimus mTOR BSC (Placebo) OS
ENRICH nimotuzumab EGFR irinotecan OS
GRANITE2 everolimus mTOR weekly paclitaxel PFS
GOLD olaparib PARP weekly paclitaxel OS
BRIGHTER BBI-608 STAT3 weekly paclitaxel OS
KEYNOTE 061 pembrolizumab PD-1 weekly paclitaxel PFS, OS in PD-L1+
2nd / 3rd GRANITE1 everolimus mTOR BSC (placebo) OS
3rd JAVELIN GASTRIC 300 avelumab PD-L1 Irinotecan/taxane OS
Apatinib Study (China only) apatinib VEGFR2 BSC (placebo) OS
3rd~ ANGEL apatinib VEGFR2 BSC (placebo) OS
ATTRACTION-02 nivolumab PD-1 BSC (placebo) OS
Global RCTs with Molecular Targeting Agents (Including PD-(L)1 Ab) for Metastatic GC
Line Study Agent Tested Targeting Control Arm Primary EP
1st ToGA (HER2) trastuzumab HER2 XP/FP OS
LOGiC(HER2) lapatinib HER2 XELOX OS
JACOB (HER2) pertuzumab HER2 XP + trastuzumab OS
AVAGAST bevacizumab VEGF XP OS
AVATAR bevacizumab VEGF XP OS
EXPAND cetuximab EGFR XP PFS
REAL-3 panitumumab EGFR EOX OS
RILOMET-1, 2 rilotumumab MET ECX, XP OS
METGastric onartuzumab MET mFOLFOX6 OS
RAINFALL ramucirumab VEGFR2 XP PFS (OS)
KEYNOTE 062 pembrolizumab PD-1 XP/FP PFS, OS
ATTRACTION-04 nivolumab PD-1 SOX/CapeOX PFS, OS
CheckMate-649 nivolumab,nivo+ipilimumab PD-1 FOLFOX/CapeOX OS in PD-L1+
GS-5745 (Gilead) andecaliximab MMP9 mFOLFOX6 OS
1st maintenance JAVELIN GASTRIC 100 avelumab PD-L1 FOLFOX/CapeOX PFS, OS
2nd TyTAN (HER2) lapatinib HER2 weekly paclitaxel OS
GATSBY (HER2) TDM-1 HER2 weekly paclitaxel OS
RAINBOW ramucirumab VEGFR2 weekly paclitaxel OS
REGARD everolimus mTOR BSC (Placebo) OS
ENRICH nimotuzumab EGFR irinotecan OS
GRANITE2 everolimus mTOR weekly paclitaxel PFS
GOLD olaparib PARP weekly paclitaxel OS
BRIGHTER BBI-608 STAT3 weekly paclitaxel OS
KEYNOTE 061 pembrolizumab PD-1 weekly paclitaxel PFS, OS in PD-L1+
2nd / 3rd GRANITE1 everolimus mTOR BSC (placebo) OS
3rd JAVELIN GASTRIC 300 avelumab PD-L1 Irinotecan/taxane OS
Apatinib Study (China only) apatinib VEGFR2 BSC (placebo) OS
3rd~ ANGEL apatinib VEGFR2 BSC (placebo) OS
ATTRACTION-02 nivolumab PD-1 BSC (placebo) OS
Global RCTs with Molecular Targeting Agents (Including PD-(L)1 Ab) for Metastatic GC
Treatment Pathways Currently under Evaluation for Gastric Cancer
EGFR: epidermal growth factor receptor; STAT3: signal transducer and activator of transcription 3Extensively Modified from Shah MA. J Clin Oncol 33:1760–1769, 2015
STAT3 ×
Immune Checkpoint Inhibitor (Nivolumab ○)
Angiogenesis (BEV ×, AFL×, RAM ○, <Apatinib ○>)
EGFR ×
MET ??
>5,000 patients are planned to be enrolled in 19 ongoing studies, with additional studies being planned
FGFR ??
HER-2 (Tmab ○, T-DM1 ×, Lapatinib ×, Pertuzumab ×)
Predicted ORR Across Tumor Types in 2L All-Comers
PFS Across Tumor Types in 2L All Comers
A Meta-Analysis to Indirectly Compare The Efficacy Profiles of Anti-PD-1/PD-L1 Monotherapy across Solid Tumors Using A Bayesian Hierarchical Model
Koneru M, et al. ASCO 2018
ORR PFS OS
Kang YK, et al. Lancet 2017
ORR PFS OS
Fuchs CS, et al. JAMA Oncol 2018
Patient,n
Events,n
mOS, months (95%CI)
12-month OS rate (95%CI)
Nivo.330 225
5.32(4.63, 6.41)
26.6(21.1, 32.4)
PLB.163 141
4.14(3.42, 4.86)
10.9(6.2, 17.0)
OS
00 2 4 6 8 10 12 14 16 18 20 22
Time, months
Pro
babi
lity
of s
urvi
val,
%
100
80
60
40
20
HR 0.63 (95%CI 0.50, 0.78)p<0.0001
Kang Y-K, et al. ASCO-GI, 2017
ATTRACTION-02 (Nivolumab) KEYNOTE-059 (Pembrolizumab)
0
0
10
20
30
40
50
60
70
80
90
100
2 4 6 8 10 12
Ove
rall
Sur
viva
l, %
14 16 18 20 22Time, months
Median OS(95% CI), mos
12-monthOS rate, %
All patients (n=259) 5.5 (4.2-6.5) 23.4
Fuchs CS, et al. ASCO, 2017Wainberg ZA, et al. ESMO, 2017
OS
Anti-PD-1 Antibody Monotherapy: Later Line for GC
N=330 N=259
N=163
Fuchs CS, et al. JAMA Oncology 2018
Q: Which is better, in earlier or later line in case of using anti-PD-(L)1 antibody
for G/GEJ Cancer?
A: Probably earlier line is better in terms of efficacy (ORR, OS).
Hui R. ASCO 2016
Brahmer JR, et al. WCLC 2017
KEYNOTE-001
KEYNOTE-024 Study Design
Reck M, et al. N Engl J Med 2016
Hui R, et al. ASCO 2016Garon EB, et al. N Engl J Med 2015
OS ORR
Lessons from NSCLC
OS
KN-59 cohort 3N = 31
KN-59 cohort 1N = 259
ATTRACTION-02N = 330
Line 1L 3L or later 3L or laterPD-L1 + All comer + - All comer + -ORR 26% 11.6% 16% 6% 11.2% - -DCR 36% 27% 34% 19% 40.3%
mPFS 3.3m 2.0m 2.1m 2.0m 1.61m - -mOS 20.7m 5.5m 5.8m 4.6m 5.3m 6.1m 5.2m
AE (Any) 77% 61% 43%AE (≧G3) 23% 18% 11%
ORR And Waterfall in KEYNOTE-059 & Attraction-02
24 patients (77%) experienceda reduction in target lesion size
Best Percentage Change in All Patients (n = 31)
–100
–80
–60
–40
–20
0
20
40
60
80
100
Cha
nge
From
Bas
elin
e, %
20% increase in tumor size
95 patients (42%) experienceda reduction in target lesion size
Best Percentage Change in All Patients (n = 224)
Wainberg ZA, et al. ESMO, 2017 Fuchs CS, et al. JAMA Oncol 2018 Kang YK, et al. Lancet 2017
Phylogenetic Tree Analyses:Clonal And Subclonal Neoantigen
Heterogeneous tumors are composed of multiple subclones and under selection pressures, such as chemotherapy, subclones with either intrinsic or acquired resistance can be selected for, allowing these subclones to dominate a tumor mass and potentially drive disease progression.
Primary tumors consist of different subclones with shared and private somatic alterations. Alterations shared by all tumor cells (A) occur early in tumorigenesis, represented by the blue trunk of the phylogenetic tree; alterations shared by tumor cells present in some regions of the tumor but not all (B and C) occur later in tumorigenesis, represented by the yellow branches of the tree; and private alterations (D–F) present in only one region of the tumor also occur later in tumorigenesis, represented by the red branches of the tree.
Jamal-Hanjani M, et al. Clin Cancer Res 21:1258-1266, 2015
Clonal Neoantigens Elicit T cell Immunoreactivity And Sensitivity to Immune Checkpoint Blockade
McGranahan N, et al. Science 351:1463-1469, 2016
A relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinoma was observed.
Sensitivity to PD-1 blockade in patients with advanced NSCLC was enhanced in tumors enriched for clonal neoantigens.
T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit.
Cytotoxic chemotherapy–induced subclonalneoantigens, contributing to an increased mutational load, were enriched in certain poor responders.
Q: What is a biomarker of anti-PD-(L)1 therapy in G/GEJ cancer?
A: 1) PD-L1 expression may be, but has not
been established robustly 2) MSI-H without doubt3) TMB probably YES, but few data in GC
Shitara K, et al. Lancet 2018
KEYNOTE-061: Overall Survival, CPS≧1%
Mok TS, et al. N Engl J Med 2009
IPASS: PFS, Gefitinib vs. CP
Is PD-L1 Expression Definite Biomarker in Anti-PD-1 Ab for GC?
Mok TS, et al. N Engl J Med 2009
IPASS (n=1218), PFS
KN-061, CPS≧1% (n=395, 67%), OS CPS≧10%
MSI-H
n=261 (21%)
n=108 (27%,18% )ITT population, n=592
n=27 (4.6% )
Shitara K, et al. Lancet 2018
0
10
20
30
40
50
60
70
80
90
100
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Prob
abili
ty o
f Sur
viva
l (%
)Overall Survival by PD-L1 Expression <1% vs ≥1%
0
10
20
30
40
50
60
70
80
90
100
0 2 4 6 8 10 12 14 16 18 20 22 24 26 28
ONO-4538
Placebo
PD-L1 <1% PD-L1 ≥1%
Hazard ratio, 0.58 (95% CI, 0.24–1.38)
Median OS, months (95% CI)
Nivolumab (n=16) 5.2 (2.8–9.4)
Placebo (n=10) 3.8 (0.8–5.0)
Ove
rall
Surv
ival
(%)
114 100 75 56 49 42 37 24 15 11 7 4 3 1 0
52 40 27 22 16 14 11 6 5 4 3 2 2 2 0
16 15 10 7 5 4 4 2 2 0 0 0 0 0 0
10 8 4 2 1 1 1 0 0 0 0 0 0 0 0Nivolumab
Placebo
Months MonthsNo. at Risk
Median OS, months (95% CI)
Nivolumab (n=114) 6.1 (4.8–8.6)Placebo (n=52) 4.2 (3.0–6.9)
Hazard ratio, 0.71 (95% CI, 0.50–1.01)
Boku N, et al. ESMO 2017
Evaluable for PD-L1 expression, n (%)≥1% vs <1%≥5% vs <5%
Nivo: 130 (39)16 (12) vs 114 (88)10 (8) vs 120 (92)
Placebo: 62 (38)10 (16) vs 52 (84)7 (11) vs 55 (89)
Among PD-L1–evaluable patients, baseline characteristics between nivolumab and placebo arms were similar
ATTRACTION-02: Nivolumab
Hellmann MD, et al. N Engl J Med. 2018
Low TMB 1Y-PFS MST 95%CINivo+Ipi 26% 3.2 M 2.7-4.3
Chemotherapy 17% 5.5 M 4.3-5.6
High TMB: defined as 10MT/Mb by Foundation One
HR 0.58 (95%C.I. 0.41-0.81)p<0.001
High TMB 1Y-PFS MST 95%CINivo+Ipi 42.6% 7.2 M 5.5-13.2
CTx 13.2% 5.5 M 4.4-5.8
No. at riskIPI+NIVO
CTx
PFS
NSCLCCTx naïve
No genetic alteration
PD-L1≧1%N=1189
PD-L1<1%N=550
IPI+NIVO(N=139)
CTx(N=160)
Lessons from NSCLC (TMB)CheckMate-227
Janjigian YY, et al. Cancer Discovery, 2018
MSI-H TMB
Megan G, et al. #4056, ASCO 2018
TMB for G/GEJ Cancer, ASCO 2018MSK-IMPACTTM (468-gene platform)
Cut off 7.3 MT/megabases
N=120 (MSI-H, N=7)
‘SCRUM JAPAN’ by OCP panel (143-gene platform)
Panel is possible instead of WES,but optimal ‘cut off’ is not established
cf: 5.0 in Foundation One Panel
Nakamura Y, et al. #12094, ASCO 2018
Q: Are there any substantial rationales regarding IO-combo therapy?
A: 1) IO + cytotoxic agents (chemotherapy)2) IO + IO3) IO + anti-angiogenic inhibitor (including
other molecular targeting agents)4) IO + radiotherapy
Combined with Chemotherapy- Is It Good or Evil?
Gandhi L, et al. AACR 2018
Emens LA, et al. Cancer Immunol Res 2015
Cytotoxic Agents Enhances Immunological Reaction around Tumor and Tumor Microenvironment
Tumor cells can upregulate expression of immune target molecules such as Fas and MHCI following irradiation. Irradiation can also normalize dilated and chaotic blood vessels to enable T cells to access tumors.
The Effects of Chemotherapy And Radiotherapy on The Tumor Microenvironment
Kershaw MH, et al. OncoImmunology, 2013
Ox can also lead to an increased proportion of proinflammatory, M1, macrophages relative to alternatively activated, M2, macrophages.
Anthracyclines can recruit APCs and enhance their differentiation to an activated phenotype, better able to present antigen to lymphocytes.
Ox can induce immunogenic cell death, which can lead to the release of tumor antigens for uptake and processing by antigen presenting cells (APC).
Gem, Ox and Paclican reduce the frequency of MDSC and/or Treginfiltrating tumors, thereby reducing their immuno-suppressive effects.
Increases in intratumoral T cells can also be achievedusing antibodies against VEGF.
Attraction-04 Part 1 Efficacy
Kang YK et al. ESMO, 2017
KN 059-Cohort 2: Best Percentage Change and Longitudinal Change in Target Lesion Size
aOnly patients with measurable disease per RECIST v1.1 by central review at baseline who had ≥1 postbaseline assessment were included (n = 25); assessment was nonevaluable for 1 patient.bLongitudinal change in the sum of the longest target lesion diameters from baseline in patients with ≥1 postbaseline assessment (n = 25).+No progressive disease at last disease assessment.
24 patients (96%) experienced a reduction in target lesion size
–100
–80
–60
–40
–20
0
20
Cha
nge
From
Bas
elin
e, %
PD-L1 positivePD-L1 expression unknownPD-L1 negative C
hang
e Fr
om B
asel
ine,
%
Best Percentage Change in All Patients (n=25)a
Cohort 2 No prior therapyPD-L1 positive or
negative
Pembrolizumab 200 mg Q3W + Cisplatin 80 mg/m2 Q3W + 5-FU 800 mg/m2 Q3W or
Capecitabine 1000 mg/m2 BID Q3Wa
aCapecitabine was administered only in Japan
Study Design
Wainberg ZA, et al. ESMO, 2017
mOS:13.8 mo
Janjigian YY, et al. ASCO 2017
Primary endpoint: • ORR per RECIST v1.1
Secondary endpoints: • OS, PFS, TTR, DOR• Safety
Exploratory endpoint: • PD-L1 tumor expression
(Dako 28-8 pharmDx assay)
Checkmate 032 EG Cohort
DOR, duration of response; EG, esophagogastric (including gastric/esophageal/gastroesophageal junction cancer); TTR, time to response.
* Nivolumab + ipilimumab administered for 4 cycles followed by nivolumab 3 mg/kg IV Q2W. † Time from first dose to data cut-off; follow-up was shorter for patients who died prior to data cut-off.
Nivolumab 3 mg/kg + Ipilimumab 1 mg/kg IV Q3W*
(NIVO 3 + IPI 1)
Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg IV Q3W*
(NIVO 1 + IPI 3)
Nivolumab 3 mg/kg IV Q2W (NIVO 3)
Western patients with advanced/metastatic EG cancer with progression on ≥1 prior chemotherapy
N = 160
Median (range) follow-up, mo†: 28 (17 to 35) 24 (21 to 33) 22 (19 to 25)
* Investigator review.# Patients with confirmed response (complete or partial response).† Patients with 0% best reduction in target lesion, including 3 patients with PD-L1 ≥1% (NIVO 3, n=2; NIVO 3 + IPI 1, n=1) and 1 patient with PD-L1 <1% (NIVO 1 + IPI 3).change truncated to 100%
†
# #
#
#
#
#
# ## # #
100
75
50
25
0
-25
-50
-75
-100Bes
t Red
uctio
n fr
om B
asel
ine
in T
arge
t Les
ions
* (%
)
#
#
##
#
100
75
50
25
0
-25
-50
-75
-100Bes
t Red
uctio
n fr
om B
asel
ine
in T
arge
t Les
ions
* (%
)
†
PD-L1 < 1% PD-L1 ≥ 1% PD-L1 not evaluable/missing
100
75
50
25
0
-25
-50
-75
-100Bes
t Red
uctio
n fr
om B
asel
ine
in T
arge
t Les
ions
* (%
)
##
#
##
#
#
† †
Best Reduction in Target Lesions
Responses were observed regardless of PD-L1 expression
ORR: 12%
Janjigian YY, et al. ASCO 2017
ORR: 24% ORR: 8%
NIVO 1 + IPI 3PD-L1–evaluable patients, 38 of 42
NIVO 3PD-L1–evaluable patients, 38 of 53
NIVO 3 + IPI 1PD-L1–evaluable patients, 34 of 41
KEYNOTE-062 (1L)Checkmate-649 (1L)
Attraction-04 (1L)
Ongoing 1L-Combination Trials
Any PD-L11st-line
N=1266Primary Endpoint: OS (PD-L1+)
PD-L1+1st-lineN=750
Primary Endpoint: PFS, OS
Primary Endpoints: PFS, OS
Any PD-L11st-lineN=650
JVDF/KN-098 Phase 1a/b Study DesignRAM + Pembro
J. Exp. Med. 2015 Vol. 212 No. 2 139–148
Herbst RS, et al. ASCO 2018
Phase 1 StudyRAM + Durvalumab
Golan T, et al. WCGC 2017
Takahari D et al. ASCO 2018
Nishina T, et al. ASCO 2018
Loi S, et al. SABCS 2017
Catenacci D VT, et al. ASCO 2018
G/GEJC (Pembro+margetuximab)
BC (Pembro+trastuzumab)
Stagg J et al. PNAS 108 : 7142-7147, 2011
Anti-HER2 Therapy for BC, G/GEJC Pretreated Trastuzumab
IO Combinations: Others
Anti-PD-(L)1 Inhibitor +
Bevacizumab: NSCLC, HCC..Lenbatinib: H&N, HCC, RCC, EC..Axitinib: RCC..BBI-608: CRC..IDO Inhibitor: TNBC, Melanoma↓..LAG-3 Inhibitor: multi-type of cancer..CCR-4 Inhibitor: HCC, PC, NSCLC, SCLC,
E/G/GEJC..M7824 (TGF-β+(avelumab)): E/G/GEJC…
Ngwa W, et al. Nat Rev Cancer 18:313-322, 2018 Sato H, et al. Nature Commun 24::1751, 2017
Durvalumab (Lung:PACIFIC trial) Nivo+SBRT (H&N)
Mcbride SM, et al. ASCO 2018Antonia SJ, et al. N Engl J Med 377: 1919-1929, 2017
Abscopal Effect RT upregulates PD-L1
IO + RT
0 5 10 15 20 25
PembrolizumabPTX
Nivolumabplacebo
pembrolizumab
pembrolizumab+XP/FP
pembrolizumab
Ipilimumabplacebo
Olaparib+PTXOlaparib
EverolimusPlacebo
ECX+rilotumumabECX
FOLFOX+onartuzumabFOLFOX
Irinotecan+nimotuzumabIrinotecan
EOC+panitumumabEOC
XP+cetuximabXP
ApatinibPlacebo
PTX+RamcirumabPTX
RamucirumabPlacebo
Ramcirumab+XP/FPXP/FP
XP+BevacizumabXP+placebo
T-DM-1PTX or DTX
PTX + LapatinibPTX
CapeOX + lapatinibCapeOX
FP/XP+trastuzumabFP/XP
FP/XP+trastuzumab+perutsuzumabFP/XP+trastuzumab
target Study Line ph OS Treatment
HER2
JACOB 1 3 ×
ToGA 1 3 〇
Logic 1 3 ×
TyTAN 2 3 ×
GATSBY 2 3 ×
VEGF/VEGFR
AVAGAST 1 3 ×
RAINFALL 1 3 ×
REGARD 2 3 〇
RAINBOW 2 3 〇
Apatinib 3 3 〇
EGFR
EXPAND 1 3 ×
REAL-3 1 3 ×
ENRICH 2 3 -
HGF RILOMET1 1 3 ×
MET METGastric 1 3 ×
mTOR GRANITE-1 2/3 3 ×
PARP GOLD 2 3 ×
CTLA-4 maintenance 1 2 ×
PD-1
KN59 ch3 1 2 -
KN59 ch2 1 2 -
KN59 ch1 3~ 2 -
ATTRACTION-02 3~ 3 〇
KN61 2 3 ×
Extensively Modified from Shitara K, Gastric Cancer 2017
OS Data from Global Trials against GC/GEJC
Summary
• Anti-PD-1 antibody monotherapy (Pembrolizumab and Nivolumab) are both active and having similar efficacy in late line of G/GEJC, but the efficacy (such as long survival) is limited to few populations.
• Anti-PD-1 antibody combined with other agents (cytotoxic, molecular targeting agent such as anti-angiogenic, and other immuno-oncological agent) demonstrates encouraging efficacy and may promise the position of earlier line therapy for G/GEJC.
• The role of PD-L1 expression and relationship between PD-L1 expression and efficacy are needed to be further investigated in G/GEJC.
• Many clinical trials in any line or any combinations are now ongoing, and these results will be confirmed as definite therapy for G/GEJC.
Acknowledgment
Thank you