GATA6 Expression as a predictor of response to perioperative chemotherapy in resectable pancreatic adenocarcinoma: A multicenter Canadian phase II study (NeoPancONE).
Authors: Kelly Deirdre , Jonker Derek J. , Ko Yoo-Joung , Karanicolas Paul Jack , Bertens Kimberly A. , Jayaraman Shiva , Abou-Khalil Jad , Moulton Carol-Anne , Raphael Michael J. , Tsang Melanie , Welch Stephen , Kavan Petr , Biagi Jim , Renouf Daniel John , Fischer Sandra , Kalimuthu Sangeetha , Khalili Korosh , Dodd Anna , Gallinger Steven , Knox Jennifer J. 
Published: January 2022

TPS638

Background: Prospective studies of the benefit of neoadjuvant chemotherapy in resectable pancreatic adenocarcinoma (PDAC) have been reported. The ideal peri-operative regimen is yet to be determined. Adjuvant FOLFIRINOX (mFFX) in resected PDAC has been proven to improve overall survival (OS) relative to adjuvant gemcitabine. An accepted perioperative approach involves delivering the majority of chemotherapy (6-8 cycles) in the pre-operative setting, while the remainder (of 12 cycles) is administered post-operatively. This pre-operative treatment period may allow for chemosensitivity assessment, and better patient selection for surgery, thereby improving R0 resection rates and reducing the frequency of early post-operative recurrence. Data from the COMPASS trial (NCT02750657) has shown that shown that low levels of the transcription factor GATA6 expression is a putative surrogate for the RNA Moffit signature and predictive of a chemoresistant phenotype in advanced PDAC. NeoPancONE will evaluate clinical outcomes and molecular biomarkers including GATA6 and radiomic biomarkers in pts with resectable PDAC treated with perioperative mFFX. Methods: NeoPancONE is a Phase 2, open-label, single arm study in pts with resectable PDAC. Tissue and serum are collected for biomarker testing, including GATA6 by FISH and IHC (1) with expression levels measured by RNAseq, and longitudinal ctDNA analysis. Pts with histologically confirmed, resectable PDAC and ECOG PS 0-1 will be recruited over 2.5 years. Resectability will be determined by central review as per NCCN guidelines. The primary objective is to evaluate disease-free survival in resectable PDAC treated with peri-operative mFFX according to baseline tumor GATA6 expression level. The ratio of GATA6-high to low is expected to be approximately 4:1[1]. Assuming 1-year disease-free survival of 65% in the GATA6-high, compared to 34% in the GATA6-low cohort, this corresponds to a hazard ratio of 2.5. With 80% power and a 5% 2-sided significance level, a total of 84 patients will be enrolled with 67 events expected in the GATA6 high cohort and 17 in GATA6 low. Participants will receive up to 6 cycles of neoadjuvant mFFX. After neoadjuvant chemotherapy, definitive surgical resection will proceed as deemed appropriate by a hepatobiliary surgeon. Post-operatively, pts will receive up to 6 cycles of adjuvant chemotherapy. Secondary objectives include determination of overall response rate, incidence of R0 resection, OS, Moffit gene expression profiling (RNAseq), ctDNA, and radiomic signatures to predict outcomes. Enrolment for NeoPancONE began in October 2020 and is being conducted at 8 sites across Canada. To date, 23 pts have been recruited. The study duration will be five years. Reference: O’Kane G M et al. Clin Can Res Sep 2020. Clinical trial information: NCT04472910.