Abstract 1551P
Background
Data driven discovery of surrogate markers of clinical endpoints has the potential utility to improve outcome for therapeutic development in PDAC. BERG’s Interrogative Biology® platform was employed to discover markers from Buffy Coat (BC) of a BPM 31510-IV Ph1 trial. The utility of these markers to predict Overall Survival (OS) was evaluated in Ph2 PDAC patients.
Methods
Proteomic markers of response were identified from treatment-naïve BC and longitudinal sampling post treatment of 104 patients in an all-comer solid tumor BPM 31510-IV Ph1. The Ph1 cohort was defined as no change/decrease (responders) or increase (non-responders) in tumor size (CT/MRI readout). Calculated slopes from tumor sizes defined treatment-response populations aligned with differentially expressed BC proteins in the Ph1 cohort were generated. To identify markers predictive of response and OS, the presence/absence of Ph1 identified BC proteins were analyzed in Ph2 PDAC patients who met criteria of adequately treated cohort (ATC- received BPM 31510-IV + gemcitabine for >30 days and had RECIST 1.1 evaluation).
Results
Of the 35 PDAC Ph2 patients, initial data demonstrate 18 met ATC criteria. To date half of the ATC population (n = 9/18, 50%) had best overall response rate of stable disease (SD) and 8/18 (44%) had SD at end of Cycle 2. Of the proteins differentially expressed in BC in phase I cohort with increasing or decreasing tumor size, two were differentially expressed in phase II patients between responders (SD) and non-responders (PD). Moreover, two proteins predictive of OS, defined as ≤2 or >2 treatment cycles, were identified, one overlapping in SD and OS.
Conclusions
BERG’s Interrogative Biology® platform applied to BC samples of BPM 31510-IV Ph1 trial has identified two potential biomarkers predictive of response and survival in PDAC patients. Candidate biomarkers had independent confirmation of prediction between SD, PD, and OS in a phase II trial. The influence of BC markers in influencing immune response in combination with BPM 31510-IV in PDAC is being investigated.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
BERG LLC.
Funding
BERG LLC.
Disclosure
V. Subbiah: Advisory/Consultancy: MedImmune; Advisory/Consultancy, Travel/Accommodation/Expenses: Helsinn Therapeutics; Advisory/Consultancy: Loxo; Advisory/Consultancy: R-Pharma-US; Advisory/Consultancy: QED Pharma; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): NanoCarrier; Research grant/Funding (institution): Northwest Biotherapeutics; Research grant/Funding (institution): Genentech/Roche ; Research grant/Funding (institution): Berg Pharma; Research grant/Funding (institution), Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Fujifilm; Research grant/Funding (institution), Travel/Accommodation/Expenses: PharmaMar; Research grant/Funding (institution): D3 Oncology Solutions; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AbbVie; Research grant/Funding (institution): Multivir; Research grant/Funding (institution): Blueprint; Research grant/Funding (institution): Medicines; Research grant/Funding (institution): LOXO; Research grant/Funding (institution): Vegenics; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Alfasigma; Research grant/Funding (institution): Agensys; Research grant/Funding (institution): Idera; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): Inhibrx; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): Turningpoint Therapeutics; Travel/Accommodation/Expenses: Medscape. M.D. Nastke, G.M. Miller, P. Shah, S. Gesta, L.O. Rodrigues, E. Granger, N.R. Narain, M.A. Kiebish, R. Sarangarajan: Full/Part-time employment: BERG LLC. M.N. Kundranda: Advisory/Consultancy: Bayer/Amgen; Research grant/Funding (institution): Celgene.