PO-443 In vitro clinical trial for pancreatic cancer patients

Abstract

IntroductionDrug treatment response prediction for cancer patients is still a challenge. It compromises clinical trials due to suboptimal selection of patients and leads to disappointing response rates for drug treatment in the clinic. Functional testing using 3D cultures of patient tumour biopsies offers the opportunity to test drug sensitivity upfront, and subsequently optimise treatment strategies for patients. Our technology based on 3D image analysis of tumour cultures accommodates accurate evaluation of drug sensitivity with small amounts of heterogeneous tumour samples. We have initiated a clinical trial to compare drug sensitivity of tumour cultures from pancreatic cancer patients, and clinical response on standard of care treatment.Material and methods3D cultures embedded in an extracellular matrix protein hydrogel are generated from tumour tissue of pancreatic cancer patients and exposed to standard-of-care therapies including FOLFIRINOX (combination of5-fluorouracil, oxaliplatin, irinotecan) and gemcitabine. An automated high content screening platform measures morphologic features of the tissue, cells and nuclei. Drug responses are reported by parameters such as tumour cell death, apoptosis, growth arrest, and local invasion. In addition, genetic characterisation of the tumour will allow further identification of relevant biomarkers. Advanced bio-informatic analysis will establish the correlation between drug sensitivity of tumour cultures with treatment response in the clinic.Results and discussionsWe present interim results of the trial (approved by LUMC ethical review board) with 3D cultured tumour material from pancreatic cancer patients. Differentiated drug responses are identified for treatment schedules including standard-of-care therapies and novel drugs that are not (yet) considered standard of care (targeting Wnt signalling pathway, PARP inhibitors).ConclusionFunctional testing is gaining interest for the development of personalised prediction of treatment outcome. Our technology enables drug sensitivity testing with standard-of-care and novel agents in 3D tumour cultures. Patient specific treatment responses can be measured per drug. Ongoing trials will establish the correlation with treatment response in the clinic. Our study results could accelerate (pre) clinical development of novel drugs. In addition, it offers opportunities to develop predictive testing for patients that are candidates for clinical trials, and to improve selection of existing drug treatment options for patients in the clinic.