Early results of the PASS-01 trial: Pancreatic adenocarcinoma signature stratification for treatment-01.

• DOI: 10.1200/jco.2024.42.17_suppl.lba4004
• Publication Date: 2024-06-05T13:28:57Z
• Authors: Jennifer J. Knox; Elizabeth M. Jaffee; Grainne M. O'Kane; Daniel King; Dan Laheru; Kenneth H. Yu; Kimberly Perez; Amber N Habowski; Robert C Grant; Sandra Fischer; Andrew Aguirre; Raymond Woo-Jun Jang; Craig E. Devoe; Eileen M. O'Reilly; Anna Dodd; Brian M. Wolpin; Xiang Y Ye; Faiyaz Notta; Steven Gallinger; David A. Tuveson
• Keywords: Risk Stratification; Stratification (seeds)

LBA4004 Background: Over 60% of patients with pancreatic ductal adenocarcinoma (PDAC) present metastatic disease. Both modified FOLFIRINOX (mFFX) and gemcitabine/nab-paclitaxel (GnP) are first-line options in advanced PDAC, however have not been compared prospectively North American patients. Moreover, biomarkers to guide selection lacking. Basal-like Classical subtypes prognostic, but their predictive impact is unknown. Patient-derived organoids (PDOs) now feasible study for drug pharmacotyping. Expedient molecular profiling additional PDO sensitivities could enable better precision choices PDAC. Methods: PASS-01 a multi-center randomized phase II trial evaluating the benefit 1 st line mFFX vs GnP de novo PDAC ECOG PS 0-1, (germline BRCA1/2, PALB2 excluded) who baseline tumor biopsies (bx) whole genome/transcriptional sequencing (WGTS) generation/pharmacotyping standard novel drugs. The primary endpoint PFS (received at least dose assigned chemo, per protocol (PP)), 136 needed reach 80% power detect difference median 7 5 months between significance level 0.3 2-sided test. Secondary endpoints include: ORR, SAEs, OS, RNA signatures GATA6 expression on outcomes. Each patient discussed board immediately following 8-week CT goal recommending 2nd-line treatment progression. Results: This accrued 160 pts 09/20 01/24, 45% Canada, 55% US 140 eligible PFS, data lock Mar 1/24 (see table). Median (PP) was 5.1 mo 4.0 (p=0.14). Best response PR/SD GnP: 29/45% 24/35% mFFX. SAEs attributed were 3% GnP, 13% 0.7% bx. OS (ITT) 9.7 8.4 mFFX, p=0.04. Of 113 PP analysis progression, 64 (57%) received (GnP, n= 30, n=34) these, correlate-guided approach delivered 32 (50%), including 21 (66%) receiving chemo 11 (34%) targeted or immunotherapy regimen. Correlative studies underway. Preliminary shows >80% successful genomes >72% signatures. include 9 % KRAS wild-type 21% PDO-drug models established 50%. Conclusions: Upfront multi-omic can be successfully incorporated into multicenter trial. While we observed improved ITT longer favouring this cohort without gBRCA 1/2 PALB2m, remains poor, 43% unable receive 2 nd line, arguing strongly development -line biomarker selected strategies. Clinical information: NCT04469556 . [Table: see text]