TEST:

PurIST℠ Test

Current regimens, such as FOLFIRINOX and gemcitabine-based combinations, are selected empirically without validated biomarkers to guide choice...Beyond regimen selection, signatures enable treatment de-escalation, optimize first-line choices, and identify multidrug-resistant tumors. Ongoing prospective trials will establish their feasibility, supporting transcriptomic profiling as a step toward precision chemotherapy in PDAC.

"Tempus AI, Inc...today announced the publication of a study in JCO Precision Oncology validating the clinical utility of the company’s PurIST® algorithmic diagnostic. The study provides the largest real-world evidence to date supporting the integration of PurIST into routine clinical care for patients with advanced PDAC, with the aim of informing first-line chemotherapy selection and improving patient outcomes."

Patients with PDAC of the PurIST classical subtype showed a significant OS benefit when treated with FFX as 1L versus GnP.

Individual patient case analyses integrating in vitro drug sensitivity profiles with clinical follow-up data suggest that f-DST using tumor organoids could guide future therapeutic strategies. In summary, tumor organoids offer insights into patient-specific responses to treatment, highlighting the potential of precision medicine in managing this challenging cancer.

Initial data suggest worse outcomes to FOLFIRINOX (FFX) compared with gemcitabine nab-paclitaxel (GnP) in basal tumors... SB subtype is a strong independent predictor of worse outcomes, irrespective of mutant KRAS allele or upfront chemotherapy regimen, and tends to remain stable between biopsies in individual patients

In summary, DeCAF subtypes were independently prognostic and associated with treatment response. DeCAF provides a powerful tool to understand the tumor microenvironment landscape of bulk tumors in patients and may facilitate the design of future clinical trials.

We evaluated the association of treatment outcomes in a Phase 2 trial of neoadjuvant nab-paclitaxel (A), gemcitabine (G), cisplatin (C), and paricalcitol (P) (NCT03138720) and a Phase 2 trial of A+G+C+hydroxychloroquine (HCQ) (NCT04669197) in patients with non-metastatic PDAC. In the study of A+G+C+P, there was a disparity in OS between patients with basal-like vs. classical tumors, in contrast to the interim results of the COMPASS and PASS-01 trials, where patients with basal-like tumors receiving A+G had similar OS compared to patients with classical tumors. Compared to prior analysis, there was no difference in OS for patients with permCAF tumors vs.

SB subtype is a strong independent predictor of worse outcomes, irrespective of upfront chemotherapy regimen. Clinical trials should investigate PC transcriptional subtypes as a biomarker.

P2; The two major molecular subtypes of pancreatic adenocarcinoma reportedly have differential response to FOLFIRINOX-based therapy...In conclusion, the PurIST Pancreatic Cancer Classifier has robust performance to classify pancreatic adenocarcinoma into basal versus classical subtypes. Clinical validation studies are underway to evaluate outcome in patients whose standard-of-care chemotherapy regimen is selected based on rapid subtype assignment (NCT04683315).

Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at metastatic stage and typically treated with fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX). These data suggest a predictive role for subtyping (transcriptomic and GATA6 IHC), though no direct causal relationship was found between GATA6 expression and chemoresistance. GATA6 immunohistochemistry should be seamlessly added to current diagnostics and integrated into upcoming clinical trials.

"Tempus AI...announced that the company’s PurISTSM algorithmic test has received a proprietary laboratory analysis (PLA) code from the American Medical Association (AMA)."

"GeneCentric Therapeutics...announced upcoming presentations at the American Association for Cancer Research Annual Meeting 2024 being held in San Diego, California from April 5-10. Presentations will include a poster describing a new colorectal cancer predictive response signature (MSS-PRS) that selects tumors not identified with conventional MSI testing but have molecular characteristics consistent with microsatellite instability, making them a potential target for immune checkpoint inhibition. A second poster presentation describes ongoing clinical validation for PurISTSM, a novel RNA-expression test developed in collaboration with Tempus. PurIST identifies patients with the classical subtype of pancreatic ductal adenocarcinoma (PDAC) that are likely to experience longer overall survival with standard of care FOLFIRINOX than patients with the basal subtype of PDAC."