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STCC Unified PD1/PD-L1 Evaluation of Response (SUPER) – A Use-Case Study of the Translational Research Integration and Support Platform

Authors
Michał Marek Hoppe1, Qing Hao Miow1, Nimmi Baby1, Carmen Yu Fei Yuen1, Yu Hui Cheng1, Vikneswari D/O Rajasegaran1, Chak Shih Cheah1, Xin Xiu Sam2, Suman Sarma3, Ngak Leng Sim3, Anders Martin Jacobsen Skanderup3, Radhika Sharma4, Yaw Chyn Lim4, Jia Hui Liew4, Sudhaharan Thankiah4, Ruifen Weng5, Xing Yi Woo6, Jeffrey Lim7, Joe Poh Sheng Yeong7, Timothy Kwang Yong Tay2, Jabed Iqbal2, Diana Gkeok Stzuan Lim8, Raghav Sundar9, Soon Thye Lim1,10, Wee Joo Chng1,4,9, Alexander Lezhava1,3, Jason Yongsheng Chan1,10 and Anand Jeyasekharan1,4,9

Affiliations

  1. Singapore Translational Cancer Consortium (STCC), Consortium for Clinical Research and Innovation, Singapore (CRIS)
  2. Department of Anatomical Pathology, Singapore General Hospital (SGH)
  3. Genome Institute of Singapore (GIS), Agency for Science, Technology and Research (A*STAR)
  4. Cancer Science Institute of Singapore, National University of Singapore (NUS)
  5. Diagnostic Development Hub (DxD Hub), Agency for Science, Technology and Research (A*STAR)
  6. Bioinformatics Institute (BII), Agency for Science, Technology and Research (A*STAR)
  7. Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR)
  8. Department of Pathology, National University Hospital (NUH)
  9. Department of Haematology-Oncology, National University Cancer Institute, Singapore (NCIS), National University Hospital (NUH)
  10. Division of Medical Oncology, National Cancer Centre Singapore (NCCS)

Background & Objectives
Immune Checkpoint Inhibitors hold a significant proportion of the cancer drug market, yet varied responses they elicit present challenges in the clinical setting. Patients who show exceptional and poor responses to this cancer treatment, provide invaluable insights into the factors determining survival outcomes. The SUPER study, a collaboration among multiple institutions, aims to develop and validate a combined assay of predictive biomarkers for PD 1/PD L1 inhibition leveraging on Singapore Translational Cancer Consortium (STCC)’s Translational and Pre-clinical Research Pipeline.

Methods & Results
The study sought to identify one hundred exceptional responders, case-control matched with one hundred hyperprogressors, to PD 1/PD L1 inhibition across diverse cancer types within two prominent cancer centers in Singapore (NCCS and NCIS). Their archival histopathological specimens were extensively profiled with a suite of genomic and proteomic assays (DNA/RNA sequencing, highly-plexed immunohistochemistry, digital spatial profiling and others) to establish a comprehensive multi-dimensional molecular data repository. This invaluable resource will serve as a foundational tool for developing biomarkers and predictive models that will impact cancer management, optimize public healthcare expenditure, and improve cancer outcomes locally and globally. The process of case identification, coupled with extensive molecular profiling, will be finalized in 2024, with resources and initial analyses slated for public release in 2025.

Results
The SUPER study stands as a prime example of conducting cutting-edge, large-scale clinical research studies involving multiple public institutions in Singapore (STCC, NCIS, NCCS, SGH, NUS, GIS, IMCB, DxD Hub, and BII). STCC, a national cancer consortium, operates as an one-stop-shop platform created to meet the demand for a synergized, nationwide translational cancer research.

Keywords
cancer, molecular profiling, PD1/PD-L1 inhibitors, biomarkers, exceptional responders