Abstract 1505P
Background
The recent phase II NEONAX trial examined PO and A Gem-nabPac CTX for rPDAC Pts. The objective of this study was to identify underlying alterations in the tumor immune microenvironment (TiME) associated with shortest (S) or longest (L) disease-free survival (DFS) and to identify corresponding biomarkers predicting CTX success.
Methods
Pts from both study arms were stratified into groups based on S- or L-DFS (n = 32, n = 8 Pts/group). PDAC tissues (surgical resection) were subjected to RNA (NanoStringTM, PanCancer IO360TM) profiling. CTX-naïve blood samples were analyzed via multiplexed ELISA (mELISA, 80-Plex ProcartaPlexTM). For feature selection via machine learning (ML), the Weka-based algorithms WrapperSubsetEval (WSE) with Naïve Bayes, J48, or a multilayer perceptron neuronal network (MLP) were used. Pts were divided into training (80%) and validation (20%) datasets and categorized by using either MLP or J48 classifiers.
Results
Comparisons of L- vs. S-DFS transcriptomics data revealed significantly increased inflammation (upregulated genes: CXCL9, SELP, CDH5), immune cell activation (enriched: NK cell cytotoxicity, activated CD8 T cells), and immune cell infiltration (CD8 T cells, NK cells) for treated (PO group) but not treatment-naïve (A group) L-TTF tumors. Screening of CTX-naïve blood samples (mELISA) detected 80 immune-related factors. Feature selection for S- vs. L-DFS prediction (n = 80 Pts; PO: n = 42, A: n = 38) revealed a panel of 8 proteins for the PO group (Naïve Bayes; CSF3, LGALS3, GZMA, CCL1, IL20, IL3, CCL7, PTX3), 6 proteins for the A group (J48; IL1A, IL1B, IL3, IL34, MIF, CCL19), and 7 proteins for the combined (c)rPDAC group (MLP; CCL21, CX3CL1, IL16, IL20, IL7, PTX3, TSLP). ML successfully predicted S-/L-DFS for the PO (via MLP), crPDAC (via MLP), and A (via J48) group (ROC-AUC (training) > 0.9, ROC-AUC (validation) > 0.9, respectively).
Conclusions
In our study, we have identified a favorable TiME for L-DFS rPDAC Pts under PO Gem-nabPac CTX. We further present minimal immune-related liquid biomarker signatures based on mELISA and ML for early prediction of Gem-nabPac CTX success in PO and A treatment settings, or for rPDAC Pts in general.
Clinical trial identification
NCT02047513; AIO Studie: AIO-PAK-0313.
Editorial acknowledgement
Legal entity responsible for the study
T. Seufferlein.
Funding
Celgene/Bristol Myers Squibb.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
1435P - Immunomodulatory effects and improved survival of PG2 plus preoperative chemoradiotherapy in patients with locally advanced esophageal cancer
Presenter: Lai-Man Mok
Session: Poster session 18
1436P - Better overall survival of male versus female patients with advanced gastric adenocarcinoma
Presenter: Minggui Pan
Session: Poster session 18
1437P - Tislelizumab (TIS) + chemotherapy (CT) vs placebo (PBO) + CT in HER2-negative advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GC/GEJC): RATIONALE-305 study minimum 3-year survival follow-up
Presenter: Marcia Cruz-Correa
Session: Poster session 18
1438P - First-line (1L) zolbetuximab + chemotherapy in patients (pts) with claudin 18.2 (CLDN18.2) +, HER2-, locally advanced (LA) unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma: A pooled final analysis of SPOTLIGHT + GLOW
Presenter: Yoon-Koo Kang
Session: Poster session 18
1439P - ABBV-400, a c-Met protein–targeting antibody-drug conjugate (ADC), in patients (pts) with advanced gastric/gastroesophageal junction adenocarcinoma (GEA): Results from a phase I study
Presenter: John Strickler
Session: Poster session 18
1440P - Neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma with camrelizumab, albumin-paclitaxel, carboplatin and apatinib (GASTO-1093): A single-arm, open-label, phase II trial
Presenter: Chao Cheng
Session: Poster session 18
1441P - Clinical application of a machine learning-based pathomics signature for predicting lymph node metastasis in early gastric cancer
Presenter: Weiyao Li
Session: Poster session 18
1442P - Correlation between intratumor HER2 heterogeneity and circulating tumor DNA in HER2 positive advanced gastric cancer: A phase Ib trial of HER2 and PD-1 dual targeted therapy (Ni-High) substudy
Presenter: Hiroki Osumi
Session: Poster session 18
1444P - Nature trumps nurture: Squamous cell carcinoma remains the leading cause of esophageal cancer in Asian-Americans
Presenter: Shubham Gulati
Session: Poster session 18