Precision Promise (PrP): Success rates of paired biopsies and biomarker testing results for metastatic pancreatic cancer (mPDAC) in a multi-center trial.

Abstract

4196 Background: PrP, a phase 2/3 Bayesian adaptive platform trial sponsored by the Pancreatic Cancer Action Network, was developed to test multiple experimental arms efficiently against common controls and explore biomarkers of response/resistance in mPDAC (Picozzi, ASCO TPS 4188, 2022). Methods: At screening, core tissue biopsies and matched blood collection were performed for first- and second-line patients (pts) with mPDAC. Week 8 (W8) core tissue biopsies and blood collection were performed for pts receiving study drug. Formalin-fixed paraffin embedded (FFPE) tissue slides were prepared at the central lab; tissue and matched blood samples were analyzed for genomic and transcriptomic analyses using Tempus xT (DNA) and xR (RNA) testing, respectively. The workflow prioritized DNA followed by RNA isolation. Results: Tissue biopsies were obtained at screening from 491 of 700 (70%) pts across 24 US sites; W8 tissue biopsies were obtained from 228 of 443 (51%) pts receiving study drug. Reasons for biopsies not being collected included: contraindicated; attempted, but no tissue obtained; pt screened out; pt stopped study drug before W8 (W8 only). 21% (103/491) screening and 32% (74/228) W8 biopsies submitted for biomarker testing contained insufficient tumor tissue for testing; 4% (20 pts) of screening and 4% (10 pts) of W8 biopsies were not processed into FFPE or testing was cancelled. Of the 368 pts with screening tissue sequenced, genomic data were generated for 83% (304 pts); 17% (64 pts) had Quantity Not Sufficient (QNS) for DNA. Transcriptomic data were generated for 49% (179 pts); in 42% (155 pts) insufficient tumor tissue remained for RNA testing and 9% (34 pts) had QNS for RNA. Of the 144 pts with W8 tissue sequenced, genomic data were generated for 71% (102 pts); 29% (42 pts) had QNS for DNA. Transcriptomic data were generated for 31% (44 pts); in 58% (84 pts) insufficient tumor tissue remained for RNA testing and 11% (16 pts) had QNS for RNA. Locations of tissue biopsies across both timepoints (719) were: 68% liver, 16% pancreas, 16% other metastatic sites. Success rates for biomarker testing across all tissue obtained was higher for liver metastases (65% DNA results; 37% RNA results) than for primary tumors in the pancreas (42% DNA results; 19% RNA results). Distribution of actionable biomarkers detected will be presented. Conclusions: These data demonstrate success rates of paired biopsy acquisition and subsequent genomic and transcriptomic analysis in a large phase 2/3 multi-center platform trial for mPDAC. Attrition was noted for biopsy collection and downstream biomarker testing at screening and more so at W8 on study drug. Biomarker testing success rates varied by tissue location. These findings along with planned data interrogation and future sample analyses will provide insights to guide future trial design and clinical decision making. Clinical trial information: NCT04229004 .