On May 25, 2017 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, reported the highlights of numerous advances in precision oncology and cancer immunotherapy using the nCounter platform that will be presented at the 53rd Annual Meeting of the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (Press release, NanoString Technologies, MAY 25, 2017, View Source [SID1234519292]). Schedule your 30 min Free 1stOncology Demo! "The breadth of nCounter-based research at this year’s ASCO (Free ASCO Whitepaper) conference demonstrates the scientific momentum and significant commercial advances that we’ve made in our key markets, most notably immuno-oncology," said Brad Gray, president and chief executive officer of NanoString. "In addition, our new Digital Spatial Profiling technology continues to demonstrate its unique value in characterizing the tumor microenvironment to inform decisions in drug development programs."
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More than 35 abstracts will be presented at the ASCO (Free ASCO Whitepaper) Annual Meeting, which is being held June 2nd through June 6th, 2017 in Chicago, Illinois. The research being presented spans a wide breadth of applications including Targeted Discovery, Biomarker Development and Clinical Practice across multiple oncology indications, including the following.
Targeted Discovery
Multidimensional spatial characterization of the tumor microenvironment (TME) in synchronous melanoma metastases (SMM) to yield insights into mixed responses to therapy in metastatic melanoma (MM) patients (pts). (Abstract # 9575)
NanoString’s new Digital Spatial Profiling research platform was used for spatial characterization of 30 immune markers and signaling proteins in melanoma patient samples to understand correlations and determinants of response.
Molecular characterization of immune-related severe adverse events (irSAE). (Abstract #3076)
NanoString Digital Spatial Profiling was used to profile the immune cell population in tissue affected by immune checkpoint inhibitors-mediated inflammation. Similarities and differences between autoimmune disease and colon-irSAEs were identified at the gene expression and proteomic levels, as regions of inflammation showed higher CD68 and PD-L1 positivity in colon-irSAE specimens versus normal colon or Crohn’s specimens, and reduced beta-catenin levels in both Crohn’s and colon-irSAE specimens relative to normal controls.
Distinct gene expression, mutational profile and clinical outcomes of V600E and V600K/R BRAF-mutant metastatic melanoma (MM). (Abstract #9541)
Gene expression and mutational profiling were used to investigate potential mechanisms explaining the observation that V600K/R metastatic melanoma has inferior response and shorter survival with MAPKi than V600E.
Biomarker Development
Correlation of constitutive PD-1 resistance in HNC with GM-CSF expression and presence of myeloid derived suppressor cells (MDSCs). (Abstract #6049)
A 638-gene immune gene expression panel was used to explore why the majority of INF-G inflamed head and neck squamous cell carcinomas (HNC) tumors do not respond to PD-1 checkpoint blockade. Constitutive resistance to PD-1 checkpoint blockade in inflamed HNC associates with expression of GM-CSF and Myeloid Derived Suppressor Cell (MDSC) markers. Strategies to deplete MDSCs, such as chemotherapy, should be considered in combination or sequentially with anti-PD-1.
Cellular immune biomarkers to prognosticate for survival to adoptive T-cell therapy in advanced nasopharyngeal cancer. (Abstract #6047)
nCounter platform and reagents were used for longitudinal modular transcriptome analysis of PBMC from patients with stage 4c nasopharyngeal carcinoma who received first line chemo-immunotherapy with the aim of identifying signatures associated with positive clinical outcomes.
Results from this study showed that 2-year survivors displayed significant decreased amounts of monocytic myeloid-derived suppressor cells (mMDSCs), compared to non-survivors.
Phase II study of durvalumab (anti-PD-L1 antibody) in combination with R-CHOP or lenalidomide plus R-CHOP in previously untreated, high-risk diffuse large B-cell lymphoma. (Abstract # TPS7573)
NanoString’s Lymphoma Subtyping Test is being used to determine Cell of Origin in an ongoing clinical trial. The primary study objective is to explore the clinical activity of durvalumab with R-CHOP in non-activated B-cell-like (non-ABC) and durvalumab with lenalidomide + R-CHOP (R2-CHOP) in ABC previously untreated DLBCL; secondary objectives are to evaluate safety and identify biomarkers predictive of clinical response.
Association of molecular subtype, proliferation, and immune genes with efficacy of carboplatin versus gemcitabine addition to taxane-based, anthracycline-free neoadjuvant chemotherapy in early triple-negative breast cancer (TNBC): Results of the randomized WSG ADAPT-TN trial. (Abstract #573)
NanoString assays combining the PAM50 breast cancer assay and immune profiling were used to characterize patients in a clinical trial. In early TNBC, basal-like subtype, higher Ki67 (by IHC), and lower HER-2 score were associated with chemo-sensitivity for both neoadjuvant arms. Chemo-resistance pathways differed between the two taxane-based combinations. The positive predictive impact of immunological genes in the nab-pac – carbo arm could influence optimal patient selection for immune-modulative therapy.
Impact of consensus molecular subtyping (CMS) on overall survival (OS) and progression free survival (PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405 (Alliance). (Abstract #3511)
CALGB 80405 was a randomized Ph3 trial showing no OS or PFS difference in mCRC pts treated with Bevacizumab (Bev) or Cetuximab (Cet) in the first line. A Nanostring platform was used to determine the CMS classification of 392 KRAS wt (codon 12 and 13) primary tumors and correlated it with OS and PFS in patients enrolled in 80405. Data suggest that CMS is associated with OS and PFS in first line therapy in mCRC patients. Preliminary data suggest that certain CMS may be associated with efficacy of Bev and Cet based chemotherapy.
Clinical Practice
Impact of the Prosigna (PAM50) assay on adjuvant clinical decision making in patients with early stage breast cancer: Results of a prospective multicenter public program. (Abstract # e12062)
In this prospective decision impact study, Prosigna results led to a 39% change in adjuvant therapy indication. Patients with initial indication of CHT were changed to HT alone in > 50% of cases. Thus, Prosigna results influenced the treatment decisions and reinforced its clinical utility in real-world settings. The intrinsic subtype classification based on IHC didn’t show to be an adequate surrogate for the genomic subtypes as determined by Prosigna.
At the 2017 ASCO (Free ASCO Whitepaper) Annual Meeting, NanoString will showcase its nCounter platform, Digital Spatial Profiling and 3D Biology capabilities at booth #20097.
Abstract # Summary Hyperlink
e23198 Molecular classification with NanoString nCounter system in triple-negative breast cancer. View Source
e23103 Molecular sequencing and gene fusion detection in non-small cell lung cancer (NSCLC) patients:
Impact of co-existing alterations. View Source
3076 Molecular characterization of immune-related severe adverse events (irSAE). View Source
8015 Pembrolizumab (Pembro) plus lenalidomide (Len) and low-dose dexamethasone (Dex)
for relapsed/refractory multiple myeloma (RRMM): Efficacy and biomarker analyses. View Source
e21030 Immune cell profiling of melanoma metastases from patients treated with TriMixDC-MEL
dendritic cell therapy in combination with ipilimumab. View Source
3509 Clinical utility of colon cancer molecular subtypes: Validation of two main colorectal molecular
classifications on the PETACC-8 phase III trial cohort. View Source
530 Effects of age, immune landscape, and response to trastuzumab (H) in HER-2 positive (HER2+)
breast cancer in NCCTG (Alliance)-N9831. View Source
TPS7573 Phase II study of durvalumab (anti-PD-L1 antibody) in combination with R-CHOP or lenalidomide
plus R-CHOP in previously untreated, high-risk diffuse large B-cell lymphoma. View Source
E12062 Impact of the Prosigna (PAM50) assay on adjuvant clinical decision making in patients with early
stage breast cancer: Results of a prospective multicenter public program. View Source
7512 Clinical and biologic covariates of outcomes in ZUMA-1: A pivotal trial of axicabtagene ciloleucel
(axi-cel; KTE-C19) in patients with refractory aggressive non-Hodgkin lymphoma (r-NHL). View Source
9575 Multidimensional spatial characterization of the tumor microenvironment (TME) in synchronous
melanoma metastases (SMM) to yield insights into mixed responses to therapy in metastatic melanoma
(MM) patients (pts). View Source
e14614 Intra-tumour heterogeneity in the regulation of immune-tolerogenic pathways in primary and metastatic
hepatocellular carcinoma (HCC). View Source
e13052 Molecular profiling of cancer outliers. View Source
e12134 Immune biomarkers and treatment (tx) outcome in hormone receptor-positive (HR+) breast cancer
(BC) patients (pts) treated with preoperative chemotherapy (preop chemo) plus bevacizumab (bev). View Source
3511 Impact of consensus molecular subtyping (CMS) on overall survival (OS) and progression free survival
(PFS) in patients (pts) with metastatic colorectal cancer (mCRC): Analysis of CALGB/SWOG 80405
(Alliance). View Source
e12134 Different patterns of non immediate allergic reaction to BRAF inhibitor in two patients with metastatic
melanoma. View Source
e20028 Novel prognostic markers for epithelioid malignant pleural mesothelioma. View Source
e21052 Different patterns of non immediate allergic reaction to BRAF inhibitor in two patients with metastatic
melanoma. View Source
e23091 Effect of bavituximab in combination with nivolumab on tumor immune response in a 3D ex vivo
system of lung cancer patients. View Source
7547 Rapid, real-time central pathology review for E1412: A novel and successful paradigm for future
National Clinical Trials Network diffuse large B cell lymphoma studies. View Source
e20050 Prognostic gene signatures for lung adenocarcinoma using digital multiplexed gene expression in
formalin-fixed paraffin embedded tissue. View Source
9541 Distinct gene expression, mutational profile and clinical outcomes of V600E and V600K/R BRAF-mutant
metastatic melanoma (MM). View Source
5591 High-intermediate risk endometrial cancer: Can gene expression predict recurrence? View Source
6047 Cellular immune biomarkers to prognosticate for survival to adoptive T-cell therapy in advanced
nasopharyngeal cancer. View Source
e12541 Identification of differentially expressed genes associated with clinical response after treatment of
breast cancer skin metastases with imiquimod. View Source
10503 Molecular alterations to predict survival and response to chemotherapy of pediatric low-grade glioma. View Source
e23090 Anti-PD1 treatment to induce M1 polarization of tumor infiltrating macrophages in a 3D ex vivo system
of lung cancer patients. View Source
8557 Biomarkers of pembrolizumab (P) activity in mesothelioma (MM): Results from a phase II trial. View Source
6049 Correlation of constitutive PD-1 resistance in HNC with GM-CSF expression and presence of myeloid
derived suppressor cells (MDSCs). View Source
511 Seven-year (yr) follow-up of adjuvant paclitaxel (T) and trastuzumab (H) (APT trial) for node-negative,
HER2-positive breast cancer (BC). View Source
529 Impact of DNA repair deficiency signature on outcomes in triple negative breast cancer (TNBC) patients
treated with AC chemotherapy (SWOG S9313). View Source
e20610 Coexistence of rearranged during transfection (RET) variants and activating EGFR mutations with their
molecular implications in lung adenocarcinomas. View Source
e23205 In silico validation of a prostate cancer recurrence prognostic signature based on pathways related to
stem cells. View Source
e13090 Characterization of germline and tumor genomic profile in unselected young black breast cancer patients. View Source
8573 Pembrolizumab in patients with recurrent thymic carcinoma: Results of a phase II study. View Source
TPS594 CORALLEEN: A phase 2 clinical trial of chemotherapy or letrozole plus ribociclib as neoadjuvant treatment
for postmenopausal patients with luminal B/HER2-negative breast cancer. View Source
11553 CCL5 expression and tumor infiltrating immune cells in triple negative breast cancer. View Source
573 Association of molecular subtype, proliferation, and immune genes with efficacy of carboplatin versus
gemcitabine addition to taxane-based, anthracycline-free neoadjuvant chemotherapy in early triple-negative
breast cancer (TNBC): Results of the randomized WSG ADAPT-TN trial. View Source