Organoid Personalized Therapeutics and the Pancreatic Adenocarcinoma Signature Stratification for treatment (PASS) – 01 trial

Froeling, Fieke E.M., Plenker, Dennis, O’Kane, Grainne, Aguirre, Andrew J., Wolpin, Brian M., Laheru, Daniel A., Saif, M Wasif, Yu, Kenneth H., Fischer, Sandra, Gallinger, Steven, Knox, Jennifer J., Jaffee, Elizabeth M., Tuveson, David A. (September 2020) Organoid Personalized Therapeutics and the Pancreatic Adenocarcinoma Signature Stratification for treatment (PASS) – 01 trial. In: The London Pancreas Workshop 2020.

DOI: 10.1016/j.pan.2020.10.008


Keywords: pancreatic cancer, patient-derived organoids, transcriptomic signatures, PASS-01 Background: Patients with advanced pancreatic ductal adenocarcinoma (PDAC) continue to have a dire prognosis and only a minority of patients is fit enough to receive second-line treatment. Using patient-derived organoids (PDOs), we have identified transcriptomic signatures of chemotherapy sensitivity that may be able to stratify patients such that they receive maximal benefit from the currently approved, first-line chemotherapy regimens [1-3]. We will now test this hypothesis in the Pancreatic Adenocarcinoma Signature Stratification for treatment (PASS) – 01 trial, which is a multi-institutional randomized phase II trial between FOLFIRINOX (mFFX) and gemcitabine/nab-paclitaxel (GA). Methods: The overall aim of PASS-01 is to evaluate biomarkers and gene signatures that may predict response to mFFX and GA. The primary objective is to determine the progression free survival (PFS) benefit of mFFX compared to GA. Using 1:1 randomization, 131 evaluable patients with untreated metastatic PDAC will be recruited to provide 80% power to detect a 2-month improvement in PFS with mFFX (one-sided alpha 0.2). Secondary and exploratory objectives include determine the objective response rate, duration of response and overall survival associated with mFFX or GA, whether the chemotherapy sensitivity signature predictions correlate with responders, if PDO transcriptomic profiles parallel those obtained from patient samples, whether GATA6 expression can serve as a biomarker of response [4], the use of serial cell free circulating tumor DNA and circulating tumour cell analysis to identify emerging or de novo resistance and evaluate biomarkers of immune-oncologic sensitivity. The main inclusion and exclusion criteria are similar to major efficacy trials, with the mandatory requirement that a minimum of 4 x 18G good quality tumour core biopsies can be safely obtainable under CT or US guidance. At progression, as per RECIST 1.1 criteria, chemotherapy sensitivity signatures (RNA) and/or PDO pharmacotyping and WGS data will be used where possible to guide second-line therapy in an effort to continually provide the most active therapeutic regimens to each patient. The trial is anticipated to open Q4 2020. Conclusions: PASS-01 will provide candidate biomarkers and gene signatures that predict response to mFFX and GA, which will be further investigated in a subsequent adaptive, stratified trial.

Item Type: Conference or Workshop Item (Paper)
Subjects: Investigative techniques and equipment > cell culture > cancer organoids
diseases & disorders > cancer > cancer types > pancreatic cancer
diseases & disorders > cancer > prognosis
CSHL Authors:
Communities: CSHL labs > Tuveson lab
Depositing User: Sasha Luks-Morgan
Date: 11 September 2020
Date Deposited: 09 Jul 2021 13:50
Last Modified: 09 Jul 2021 13:50

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