Synergistic antitumor effect of the anti‑ErbB2 antibodies ...
Margetuximab (M) and Pembrolizumab (P) in HER2 ... · p=0.023 p=0.043 ERBB2/HER2 Gastric Cancer GEJ...
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Evaluation of Tumor Microenvironment Identifies Immune Correlates of Response to Combination Immunotherapy with Margetuximab (M) and Pembrolizumab (P) in HER2+ Gastroesophageal Adenocarcinoma (GEA) S. Rutella 1 , S.E. Church 2 , J. Vadakekolathu 1 , S. Reeder 1 , A. Sullivan 2 , S. Warren 2 , J. Baughman 3 , J. Muth 3 , H. Park 4 , H. Uronis 5 , Y-K. Kang 6 , M. Ng 7 , P. Enzinger 8 , K.W. Lee 9 , K. Huber 3 , A. Wynter-Horton 3 , D. Li 3 , Y-J. Bang 10 , J. Davidson-Moncada 3 , D. Catenacci 11 1 John van Geest Cancer Research Centre, Nottingham Trent University, United Kingdom; 2 NanoString Technologies Inc., Seattle, WA; 3 MacroGenics Inc., Rockville, MD; 4 Washington University School of Medicine, St. Louis, MO; 5 Duke University Medical Center, Durham, NC; 6 Asan Medical Center, Seoul, South Korea; 7 National Cancer Centre Singapore, Singapore; 8 Dana-Farber Cancer Institute, Boston, MA; 9 Seoul National University Bundang Hospital, Seongnam, South Korea; 10 Seoul National University Hospital, Seoul, South Korea; 11 The University of Chicago Medical Center and Biological Sciences, Chicago, IL Abstract #2547 Presented at the 2019 Annual Congress of the European Society for Medical Oncology, September 27–October 1, 2019, Barcelona, Spain [email protected] Background ■ Gastric cancer is the fifth most common cancer and the third most common cause of cancer deaths worldwide ■ Despite improvements in treatment, the 5-year survival of patients with GEA is disappointing ■ Individual molecular subtypes of GEA display preferential responses to PD-1 blockade ■ Margetuximab is an investigational Fc-optimized anti-HER2 monoclonal antibody being tested in combination with pembrolizumab in HER2+ GEA post trastuzumab Materials and Methods ■ 92 patients with advanced, relapsed/refractory HER2+ gastric cancer (GC) and gastroesophageal junction (GEJ) cancer were treated with margetuximab + pembrolizumab in the CP-MGAH22-05 study ■ 55 pre-treatment tumor samples were assessed by NanoString’s PanCancer IO360™ (IO360) gene expression assay (for research use only) 1 – IO360 signature scores were calculated and are presented as fold changes (FC) and analyzed by unpaired t test ■ Associations examined include: – Overall inflamed tumor microenvironment (TME) – Complete response (CR) n=1, partial response (PR) n=13, stable disease (SD) n=23, progressive disease (PD) n=18 – Immunohistochemistry (IHC) status for PD-L1 (positive n=25, versus negative n=27) and HER2 (IHC3+ n=45, versus IHC2+ n=10) – Tumor location (GC n=46, versus GEJ cancer, n=9) Results Best Response by HER2 Expression and Tumor Site * * * * * * * * -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 40 50 60 70 80 90 100 110 120 130 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120 Weeks Since Treatment Initiation *** -6 -2 2 6 10 14 18 22 26 30 34 38 42 46 50 Change in Target and New Lesions from Baseline (%) First new lesion Ongoing Change from Baseline (%) HER2 (IHC3+) GC HER2 (IHC2+) GC HER2 (IHC3+) GEJ HER2 (IHC2+) GEJ Treatment ongoing Includes only patients evaluated per assay * HER2 (IHC3+) Gastric Cancer -100 -90 -80 -70 -60 -50 -40 -30 -20 -10 0 10 20 30 40 50 60 70 80 90 100 110 120 130 Change from Baseline (%) ERBB2amp/PD-L1+ GC ERBB2amp/PD-L1- GC ERBB2neg/PD-L1+ GC ERBB2neg/PD-L1- GC * * * * * ORR 32.7% (18/55) DCR 69.1% (38/55) mOS 14.6 months (95% CI 10.55, NR) Treatment ongoing Includes only patients evaluated per assay * ■ Increased response rate in patients with ERBB2amp, a surrogate for HER2 expression, post trastuzumab ■ Double positive population (ERBB2amp/PD-L1+) most sensitive population to combination therapy Baseline HER2 Immunohistochemistry HER2 IHC PFS HER2 IHC2+ (n=21) HER2 IHC3+ (n=71) # of events 21 57 Median PFS (95% CI) 1.38 months (1.31–1.61) 4.34 months (2.60–5.62) HR by Cox model, 0.32; 95% CI, 0.17–0.53; Log-rank P<0.0001 6-month PFS rate (95% CI) 4.8% (0.3–19.7) 38% (26.4–49.5) 12-month PFS rate (95% CI) NA 24% (13.8–35.0) HER2 IHC OS HER2 IHC2+ (n=21) HER2 IHC3+ (n=71) # of events 19 37 Median OS (95% CI) 5.6 months (2.99–11.53) 13.9 months (10.55–20.47) HR by Cox model, 0.30; 95% CI, 0.17–0.53; Log-rank P<0.0001 12-month OS rate (95% CI) 24.4% (8.2–45.3) 59.8% (44.6–70.8) 21 20 5 4 4 2 1 1 1 0 71 68 43 37 35 29 21 20 18 15 15 13 9 8 7 7 6 5 4 4 2 2 2 2 1 1 1 0 IHC3+ IHC2+ 0.0 2 4 6 8 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 0.2 0.4 0.6 0.8 1.0 IHC3+ IHC2+ Survival Probability PFS Months from Treatment Initiation IHC3+ IHC2+ 0 12 34 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 21 20 18 15 14 11 10 9 7 5 5 5 4 4 3 1 0 71 71 77 63 61 60 55 46 39 37 31 29 25 22 20 19 16 14 11 8 6 5 3 3 3 2 2 1 1 0 0.0 2 4 6 8 0 0.2 0.4 0.6 0.8 1.0 Survival Probability IHC3+ IHC2+ OS Months from Treatment Initiation ERBB2/HER2 Expression is Associated with HER2 3+ IHC ERBB2 Expression 14 12 10 8 6 ERBB2/HER2 2+ 3+ cCR cPR PD SD ■ ERBB2 mRNA expression was 5.6 times higher in patients with HER2 IHC3+ compared with IHC2+ tumors PD-L1 Positive IHC Is Associated with Interferon-related Signatures PD-L1 LAG3 PD-L1 Expression LAG3 Expression Negative Positive Negative Positive IDO1 IFN-γ Signaling TIS ID01 Expression IFN-γ Signaling TIS cCR cPR PD SD Negative Positive Negative Positive Negative Positive 10 9 8 7 6 5 5 4 3 2 4 3 8 7 6 5 4 3 7 6 5 4 3 8.5 8.0 7.5 7.0 6.5 6.0 5.5 5.0 Change from PD-L1 Negative -1.5 -1 -0.5 0 0.5 1 1.5 2 Down from Negative log2 fold-change Up from Negative Proliferation Stroma Lymphoid Myeloid Endothelial cells APM MHC2 IFN gamma Cytotoxicity Immunoproteasome Apoptosis Inflam chemokines Hypoxia MAGEs Glycolysis IFN downstream Myeloid inflammation B cells CD45 CD8 T cells Cytotoxic cells DC Exhausted CD8 Macrophages Mast cells Neutrophils NK CD56dim cells NK cells T cells Th1 cells Treg TIS ARG1 NOS2 IDO1 PD-L1 CTLA4 IL10 PD-L2 B7-H3 TIGIT TGF-Beta PD-1 MMR loss APM loss JAK-STAT loss ERBB2 JAK2 JAK1 IFNGR1 IRF1 IFNGR2 LAG3 TNFRSF9 TNFRSF10B Higher in Pos Higher in Neg ■ PD-L1-positive tumors had higher expression of PD-L1, IFN-γ signaling, LAG3, IDO1, inflammatory chemokine and tumor inflammation signature (TIS) scores ERBB2/HER2 Expression is Associated with Gastric Tumors ERBB2 Expression 14 12 10 8 6 ERBB2/HER2 GC GEJ cCR cPR PD SD ■ Gastric tumors xpressed higher levels of ERBB2 (5.25 FC, p<0.001) compared with GEJ tumors Differential Gene Expression in Gastric vs. GEJ Tumors -log10 (p-value) 0 1 2 3 4 log2 fold-change, Tumor.Location = GEJ vs. GC 0 -1.0 -0.5 1 2 Higher in GEJ Higher in GC False discovery rate = 0.5 False discovery rate = 0.1 False discovery rate = 0.05 Gene/Signature Fold Change p-value IFITM1 2.420 0.0001 MYC 1.820 0.0006 ERBB2 5.252 0.0009 STAT3 1.687 0.0026 DUSP1 2.699 0.0059 S100A8 4.841 0.0065 CDH1 1.574 0.0105 FBP1 1.863 0.0108 IFITM2 1.653 0.0121 API5 1.257 0.0148 S100A9 4.036 0.0172 HNF1A 1.695 0.0187 PRLR 2.073 0.0193 EGR1 1.888 0.0205 MKI67 1.538 0.0244 DUSP5 1.787 0.0251 SGK1 1.522 0.0277 NFIL3 1.435 0.0295 CD209 1.632 0.0307 FOSL1 1.804 0.0316 EPCAM 1.554 0.0337 RELA 1.224 0.0355 LAMB3 1.651 0.0365 MRPL19 1.187 0.0441 EDN1 1.501 0.0452 NFKBIA 1.473 0.0462 CDKN1A 1.554 0.0464 ■ GEJ tumors had lower expression of ERBB2 and higher expression of IFITM1, MYC and STAT3, and less clinical responses Discussion ■ We show for the first time that GEA with high ERBB2 expression have an inflamed TME ■ Our initial data describe potential immunologic differences between GC and GEJ tumors Reference 1. This study was sponsored by MacroGenics, Inc. Copies of this poster obtained through QR (Quick Response) and/or text key codes are for personal use only and may not be reproduced without written permission of the authors. NCT02689284 ERBB2/HER2 Expression is Associated with Response ERBB2 Expression 14 12 10 8 6 PD SD c*PR/CR p=0.023 p=0.043 ERBB2/HER2 Gastric Cancer GEJ Cancer ■ ERBB2 mRNA expression significantly correlated with response, being 5.13 times higher in patients achieving CR/PR compared with patients with PD *c: Confirmed Differential Expression Associated with Anti-Tumor Activity -log10 (p-value) 0.0 0.5 1.0 1.5 2.0 log2 fold-change, BOR.NS = CR/PR/SD vs. PD 0 -1.5 -1.0 -0.5 0.5 1.0 1.5 Higher in R Higher in PD False discovery rate = 0.5 False discovery rate = 0.1 False discovery rate = 0.05 Gene Fold Change SE p-value ERBB2 3.145 0.549 0.004 GMIP 1.357 0.155 0.006 WNT7B 2.493 0.516 0.014 CXCL5 3.006 0.660 0.020 SLC1A5 0.771 0.162 0.024 CD47 1.305 0.171 0.029 CD247 1.459 0.250 0.034 TICAM1 1.220 0.136 0.040 ELOB 1.321 0.197 0.046 CCND2 0.697 0.262 0.051 ■ ERBB2 mRNA expression significantly correlated with anti-tumor activity, being 3.1 times higher (p=0.004) in patients achieving CR/PR/SD compared with patients with PD ERBB2/HER2 Expression is Associated with Anti-Tumor Activity Gastric Cancer GEJ Cancer ERBB2 Expression True Positive Rate (Sensitivity) for Detecting BOR*.NS = CR/PR/SD PD 14 12 10 8 6 1.0 0.8 0.6 0.4 0.2 0.0 1.0 0.8 0.6 0.4 0.2 0.0 AUC = 0.754 CR/PR/SD ERBB2/HER2 ERBB2 Expression False Positive Rate (1 - Specificity) for Detecting BOR*.NS = CR/PR/SD ■ ERBB2 expression was associated with anti-tumor activity of margetuximab + pembrolizumab with an AUC of 0.754 *Best overall response NK CD56dim Cell Abundance Trends Higher with Anti-Tumor Activity Gastric Cancer GEJ Cancer NK CD56dim Cell Abundance NK CD56dim Cells Abundance 8 7 6 5 4 3 PD CR/PR/SD NK CD56dim Genes IL21R KIR2DL3 KIR3DL1 KIR3DL2 ■ Tumor control was associated with a modest increase in CD56dim NK cells (p=0.092)
Transcript of Margetuximab (M) and Pembrolizumab (P) in HER2 ... · p=0.023 p=0.043 ERBB2/HER2 Gastric Cancer GEJ...
Evaluation of Tumor Microenvironment Identifies Immune Correlates of Response to Combination Immunotherapy with Margetuximab (M) and Pembrolizumab (P) in HER2+ Gastroesophageal Adenocarcinoma (GEA)
S. Rutella1, S.E. Church2, J. Vadakekolathu1, S. Reeder1, A. Sullivan2, S. Warren2, J. Baughman3, J. Muth3, H. Park4, H. Uronis5, Y-K. Kang6, M. Ng7, P. Enzinger8, K.W. Lee9, K. Huber3, A. Wynter-Horton3, D. Li3, Y-J. Bang10, J. Davidson-Moncada3, D. Catenacci11
1John van Geest Cancer Research Centre, Nottingham Trent University, United Kingdom; 2NanoString Technologies Inc., Seattle, WA; 3MacroGenics Inc., Rockville, MD; 4Washington University School of Medicine, St. Louis, MO; 5Duke University Medical Center, Durham, NC; 6Asan Medical Center, Seoul, South Korea; 7National Cancer Centre Singapore, Singapore; 8Dana-Farber Cancer Institute, Boston, MA; 9Seoul National University Bundang Hospital, Seongnam, South Korea; 10Seoul National University Hospital, Seoul, South Korea; 11The University of Chicago Medical Center and Biological Sciences, Chicago, IL
Abstract #2547
Presented at the 2019 Annual Congress of the European Society for Medical Oncology, September 27–October 1, 2019, Barcelona, Spain [email protected]
Background■■ Gastric cancer is the fifth most common cancer and the third most common cause of cancer deaths worldwide■■ Despite improvements in treatment, the 5-year survival of patients with GEA is disappointing■■ Individual molecular subtypes of GEA display preferential responses to PD-1 blockade■■ Margetuximab is an investigational Fc-optimized anti-HER2 monoclonal antibody being tested in combination with pembrolizumab in HER2+ GEA post trastuzumab
Materials and Methods■■ 92 patients with advanced, relapsed/refractory HER2+ gastric cancer (GC) and gastroesophageal junction (GEJ) cancer were treated with margetuximab + pembrolizumab in the CP-MGAH22-05 study ■■ 55 pre-treatment tumor samples were assessed by NanoString’s PanCancer IO360™ (IO360) gene expression assay (for research use only)1
– IO360 signature scores were calculated and are presented as fold changes (FC) and analyzed by unpaired t test
■■ Associations examined include: – Overall inflamed tumor microenvironment (TME) – Complete response (CR) n=1, partial response (PR) n=13, stable disease (SD) n=23, progressive disease (PD) n=18 – Immunohistochemistry (IHC) status for PD-L1 (positive n=25, versus negative n=27) and HER2 (IHC3+ n=45, versus IHC2+ n=10) – Tumor location (GC n=46, versus GEJ cancer, n=9)
Results
Best Response by HER2 Expression and Tumor Site
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* *
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-100-90-80-70-60-50-40-30-20-10
0102030405060708090
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0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100 105 110 115 120Weeks Since Treatment Initiation
***-6-226
1014182226303438424650
Chan
ge in
Tar
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and
New
Les
ions
from
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elin
e (%
)
First new lesionOngoing
Chan
ge fr
om B
asel
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(%)
HER2 (IHC3+) GCHER2 (IHC2+) GCHER2 (IHC3+) GEJHER2 (IHC2+) GEJTreatment ongoingIncludes only patients evaluated per assay
*
HER2 (IHC3+) Gastric Cancer
-100-90-80-70-60-50-40-30-20-10
0102030405060708090
100110120130
Chan
ge fr
om B
asel
ine
(%)
ERBB2amp/PD-L1+ GCERBB2amp/PD-L1- GCERBB2neg/PD-L1+ GCERBB2neg/PD-L1- GC
*
*
*
*
*
ORR 32.7% (18/55)DCR 69.1% (38/55)mOS 14.6 months (95% CI 10.55, NR)
Treatment ongoingIncludes only patients evaluated per assay
*
■■ Increased response rate in patients with ERBB2amp, a surrogate for HER2 expression, post trastuzumab■■ Double positive population (ERBB2amp/PD-L1+) most sensitive population to combination therapy
Baseline HER2 ImmunohistochemistryHER2 IHC PFS HER2 IHC2+
(n=21)HER2 IHC3+
(n=71)
# of events 21 57
Median PFS (95% CI)
1.38 months (1.31–1.61)
4.34 months (2.60–5.62)
HR by Cox model, 0.32; 95% CI, 0.17–0.53; Log-rank P<0.0001
6-month PFS rate (95% CI)
4.8% (0.3–19.7)
38% (26.4–49.5)
12-month PFS rate (95% CI) NA 24%
(13.8–35.0)
HER2 IHC OS HER2 IHC2+ (n=21)
HER2 IHC3+ (n=71)
# of events 19 37
Median OS (95% CI)
5.6 months (2.99–11.53)
13.9 months (10.55–20.47)
HR by Cox model, 0.30; 95% CI, 0.17–0.53; Log-rank P<0.0001
12-month OS rate (95% CI)
24.4% (8.2–45.3)
59.8% (44.6–70.8)
21 20 5 4 4 2 1 1 1 071 68 43 37 35 29 21 20 18 15 15 13 9 8 7 7 6 5 4 4 2 2 2 2 1 1 1 0IHC3+
IHC2+
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PFS Months from Treatment Initiation
IHC3+IHC2+
0 1 2 3 4 5 6 7 8 9 10 11 12 13 1415 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30
21 20 18 15 14 11 10 9 7 5 5 5 4 4 3 1 071 71 77 63 61 60 55 46 39 37 31 29 25 22 20 19 16 14 11 8 6 5 3 3 3 2 2 1 1 0
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IHC3+IHC2+OS Months from Treatment Initiation
ERBB2/HER2 Expression is Associated with HER2 3+ IHC
ERBB
2 Ex
pres
sion
14
12
10
8
6
ERBB2/HER2
2+ 3+
cCRcPRPDSD
■■ ERBB2 mRNA expression was 5.6 times higher in patients with HER2 IHC3+ compared with IHC2+ tumors
PD-L1 Positive IHC Is Associated with Interferon-related Signatures
PD-L1 LAG3
PD-L
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pres
sion
LAG
3 Ex
pres
sion
Negative Positive Negative Positive
IDO1 IFN-γ Signaling TIS
ID01
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IFN
-γ S
igna
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TIS
cCR cPR PD SDNegative Positive Negative Positive Negative Positive
10
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4
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7
6
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Change from PD-L1 Negative
-1.5 -1 -0.5 0 0.5 1 1.5 2Down from Negative � log2 fold-change � Up from Negative
ProliferationStromaLymphoidMyeloidEndothelial cellsAPMMHC2IFN gammaCytotoxicityImmunoproteasomeApoptosisInflam chemokinesHypoxiaMAGEsGlycolysisIFN downstreamMyeloid inflammationB cellsCD45CD8 T cellsCytotoxic cellsDCExhausted CD8MacrophagesMast cellsNeutrophilsNK CD56dim cellsNK cellsT cellsTh1 cellsTregTISARG1NOS2IDO1PD-L1CTLA4IL10PD-L2B7-H3TIGITTGF-BetaPD-1MMR lossAPM lossJAK-STAT lossERBB2JAK2JAK1IFNGR1IRF1IFNGR2LAG3TNFRSF9TNFRSF10B
Higher in PosHigher in Neg
■■ PD-L1-positive tumors had higher expression of PD-L1, IFN-γ signaling, LAG3, IDO1, inflammatory chemokine and tumor inflammation signature (TIS) scores
ERBB2/HER2 Expression is Associated with Gastric Tumors
ERBB
2 Ex
pres
sion
14
12
10
8
6
ERBB2/HER2
GC GEJ
cCRcPRPDSD
■■ Gastric tumors xpressed higher levels of ERBB2 (5.25 FC, p<0.001) compared with GEJ tumors
Differential Gene Expression in Gastric vs. GEJ Tumors
-log1
0 (p
-val
ue)
0
1
2
3
4
log2 fold-change, Tumor.Location = GEJ vs. GC0-1.0 -0.5 1 2
Higher in GEJHigher in GC
False discovery rate = 0.5False discovery rate = 0.1False discovery rate = 0.05
Gene/Signature Fold Change p-value
IFITM1 2.420 0.0001MYC 1.820 0.0006
ERBB2 5.252 0.0009STAT3 1.687 0.0026DUSP1 2.699 0.0059S100A8 4.841 0.0065CDH1 1.574 0.0105FBP1 1.863 0.0108
IFITM2 1.653 0.0121API5 1.257 0.0148
S100A9 4.036 0.0172HNF1A 1.695 0.0187PRLR 2.073 0.0193EGR1 1.888 0.0205MKI67 1.538 0.0244DUSP5 1.787 0.0251SGK1 1.522 0.0277NFIL3 1.435 0.0295CD209 1.632 0.0307FOSL1 1.804 0.0316EPCAM 1.554 0.0337RELA 1.224 0.0355
LAMB3 1.651 0.0365MRPL19 1.187 0.0441
EDN1 1.501 0.0452NFKBIA 1.473 0.0462CDKN1A 1.554 0.0464
■■ GEJ tumors had lower expression of ERBB2 and higher expression of IFITM1, MYC and STAT3, and less clinical responses
Discussion■■ We show for the first time that GEA with high ERBB2 expression have an inflamed TME■■ Our initial data describe potential immunologic differences between GC and GEJ tumors
Reference1.
This study was sponsored by MacroGenics, Inc. Copies of this poster obtained through QR (Quick Response) and/or text key codes are for personal use only and may not be reproduced without written permission of the authors.
NCT02689284
ERBB2/HER2 Expression is Associated with Response
ERBB
2 Ex
pres
sion
14
12
10
8
6
PD SD c*PR/CR
p=0.023p=0.043
ERBB2/HER2Gastric CancerGEJ Cancer
■■ ERBB2 mRNA expression significantly correlated with response, being 5.13 times higher in patients achieving CR/PR compared with patients with PD
*c: Confirmed
Differential Expression Associated with Anti-Tumor Activity
-log1
0 (p
-val
ue)
0.0
0.5
1.0
1.5
2.0
log2 fold-change, BOR.NS = CR/PR/SD vs. PD0-1.5 -1.0 -0.5 0.5 1.0 1.5
Higher in RHigher in PD
False discovery rate = 0.5False discovery rate = 0.1False discovery rate = 0.05
Gene Fold Change SE p-valueERBB2 3.145 0.549 0.004
GMIP 1.357 0.155 0.006
WNT7B 2.493 0.516 0.014
CXCL5 3.006 0.660 0.020
SLC1A5 0.771 0.162 0.024
CD47 1.305 0.171 0.029
CD247 1.459 0.250 0.034
TICAM1 1.220 0.136 0.040
ELOB 1.321 0.197 0.046
CCND2 0.697 0.262 0.051
■■ ERBB2 mRNA expression significantly correlated with anti-tumor activity, being 3.1 times higher (p=0.004) in patients achieving CR/PR/SD compared with patients with PD
ERBB2/HER2 Expression is Associated with Anti-Tumor Activity
Gastric CancerGEJ Cancer
ERBB
2 Ex
pres
sion
True
Pos
itiv
e Ra
te (S
ensi
tivi
ty)
for
Det
ecti
ng B
OR*
.NS
= CR
/PR/
SD
PD
14
12
10
8
6
1.0
0.8
0.6
0.4
0.2
0.0
1.0 0.8 0.6 0.4 0.2 0.0
AUC = 0.754
CR/PR/SD
ERBB2/HER2 ERBB2 Expression
False Positive Rate (1 - Specificity)for Detecting BOR*.NS = CR/PR/SD
■■ ERBB2 expression was associated with anti-tumor activity of margetuximab + pembrolizumab with an AUC of 0.754
*Best overall response
NK CD56dim Cell Abundance Trends Higher with Anti-Tumor Activity
Gastric CancerGEJ Cancer
NK CD56dim Cell Abundance
NK
CD56
dim
Cel
ls A
bund
ance 8
7
6
5
4
3
PD CR/PR/SD
NK CD56dim Genes
IL21R
KIR2DL3
KIR3DL1
KIR3DL2
■■ Tumor control was associated with a modest increase in CD56dim NK cells (p=0.092)
