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ePoster Display

1485P - Identification of novel protein biomarkers for FOLFIRINOX-based chemotherapy response in advanced pancreatic adenocarcinoma using patient omics and Bayesian AI

Date

16 Sep 2021

Session

ePoster Display

Presenters

A. Moser

Citation

Annals of Oncology (2021) 32 (suppl_5): S1084-S1095. 10.1016/annonc/annonc709

Authors

A.J. Moser1, M. Kiebish2, R. Sarangarajan3, N.M. Chand4, G. Miller4, L. Rodrigues4, P. Shah2, R. Searfoss2, K. Ofori-Mensa,2, V. Tolstikov2, B. Greenwood2, V. Bussberg2, E.M. Grund3, C. DeCicco1, E. Granger2, N.R. Narain2

Author affiliations

  • 1 Surgical Oncology Dept., Harvard Medical School, 02115 - Boston/US
  • 2 Precision Medicine Department, Berg LLC, 01701 - Framingham/US
  • 3 Biosystems Dept., Berg, LLC, 01701 - Framingham/US
  • 4 Analytics, Berg LLC, 01701 - Framingham/US
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Abstract 1485P

Background

FOLFIRINOX-based chemotherapy regimens are considered standard of care for advanced pancreatic cancer and treatment options become limited once patients are refractory to this initial treatment. The overwhelming risk of standard of care treatment failure for advanced pancreatic cancer highlights the need to identify biomarkers predictive of treatment-failure to improve clinical outcomes and provide alternative options.

Methods

Project Survival (PS), NCT02781012, is a longitudinal (6 yrs) prospective clinical trial of 452 patients, in which 34 patients with pancreatic ductal adenocarcinoma (PDAC) treated with FOLFIRINOX based regimen were identified. Median overall survival (OS) was 266 days. Multi-omic (global quantitative proteomics, metabolomics, structural lipidomics, and signaling lipidomics) analysis of plasma and buffy coat (proteomics only) were assessed for quantitative differences. Differential analysis of patients surviving less than or greater than 266 days identified 260 analytes (p < 0.05) between OS < 266 days to cohort with OS > 266 days respectively.

Results

To investigate the utility of these markers we evaluated multi-omic analysis in a completed clinical trial investigating BPM31510-IV (NCT# 02650804), which would represent an independent cohort of 42 PDAC subject’s refractory to FOLFIRINOX at baseline of the phase II clinical trial. BPM31510 is an ubidecarenone-lipid conjugate nanodispersion formulation that was being investigated with GEMCITABINE for the treatment of PDAC patients. Of the 260 analytes identified in the FOLFIRINOX PDAC group from PS, 4 proteins in buffy coat demonstrated utility in stratifying response to treatment based on length of survival when the markers were measured at baseline prior to treatment. These candidate markers are involved in Keratin regulated processes, WNT signaling, and cell cycle regulation.

Conclusions

The expression of these candidate markers in additional cohorts will be further assessed to demonstrate the utility of the panel for early prediction of therapeutic response in the highly refractive PDAC population.

Clinical trial identification

NCT02781012.

Editorial acknowledgement

Legal entity responsible for the study

Berg LLC.

Funding

Berg LLC.

Disclosure

A.J. Moser: Non-Financial Interests, Institutional, Research Grant: Berg LLC. M. Kiebish: Financial Interests, Personal, Full or part-time Employment: Berg LLC. R. Sarangarajan: Financial Interests, Personal, Full or part-time Employment: Berg LLC. N.M. Chand: Financial Interests, Personal, Full or part-time Employment: Berg LLC. G. Miller: Financial Interests, Personal, Full or part-time Employment: Berg LLC. L. Rodrigues: Financial Interests, Personal, Full or part-time Employment: Berg LLC. P. Shah: Financial Interests, Personal, Full or part-time Employment: Berg LLC. R. Searfoss: Financial Interests, Personal, Full or part-time Employment: Berg LLC. K. Ofori-Mensa,: Financial Interests, Personal, Full or part-time Employment: Berg LLC. V. Tolstikov: Financial Interests, Personal, Full or part-time Employment: Berg LLC. B. Greenwood: Financial Interests, Personal, Full or part-time Employment: Berg LLC. V. Bussberg: Financial Interests, Personal, Full or part-time Employment: Berg LLC. E.M. Grund: Financial Interests, Personal, Full or part-time Employment: Berg LLC. C. DeCicco: Financial Interests, Institutional, Research Grant: Berg LLC. E. Granger: Financial Interests, Personal, Full or part-time Employment: Berg LLC. N.R. Narain: Financial Interests, Personal, Full or part-time Employment: Berg LLC.

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