TEST:

PurIST℠ Test

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

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.

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.

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."

Analysis of a phase Ib trial FOLFIRINOX in combination with a CCR2 inhibitor (PF-04136309; NCT01413022) , we found that in patients with classical tumors, increasing permCAF probability was associated with response (r = -0.688, p<0.001)...DeCAF subtypes are associated with histological subtype in MESO (p = 0.021) and grade in KIRC (p = 0.056). Taken together, DeCAF subtypes explain the role of CAF subtypes in patients, provide a foundation for the translation of preclinical studies, and facilitate the design of future therapeutic approaches and clinical trials.

In this post-hoc analysis study, we examine whether the PurIST subtypes can distinguish patients likely to respond to FOLFIRINOX (FFX) versus Gemcitabine + nab-paclitaxel (GnP). A cohort of de-identified PDAC patients was selected from the Tempus Oncology Database following an IRB-approved protocol... In this real-world cohort of advanced PDAC patients, we showed that classical patients with low ECOG scores had superior OS with 1L FFX treatment compared to 1L GnP. These findings demonstrate the potential for PurIST to aid in optimal treatment selection for patients with advanced PDAC.

Classical and restCAF subtypes are associated with the most favorable response to neoadjuvant FOLFIRINOX as evidenced by lower T and N stages with treatment. Better locoregional response to systemic therapy may lead to better overall survival in these subtypes. Molecular subtyping of PDAC for both the tumor and tumor microenvironment may be important steps in selecting first-line therapy for patients with this deadly disease.Learning Objectives: Upon completion, participant will be able to distinguish differences between tumor and tumor microenvironment subtypes in pancreatic cancer.

P2; N=41 --> 87 | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Jun 2024 --> Jun 2026

Background Current therapeutic options for patients with a pancreatic ductal adenocarcinoma (PDAC) implicate monotherapy (gemcitabine) or combined therapies (modified FOLFIRINOX)...Methods To extract biologically relevant signatures for 5FU, oxaliplatin and irinotecan, we integrated transcriptomic data from patient-derived primary cell cultures (PDC), patients-derived organoids (PDO) and patient-derived xenografts (PDX) with their corresponding chemo-response profiles to capture the biological components responsible for the response to each drug...However, we observed in a multivariate Cox regression that our model based on independent signatures displayed higher predictive value for the OS and PFS. Conclusions We developed three novel transcriptome-based signatures which define sensitivity for each mFFX components that can be used to rationalize the administration of the mFFX regimen and could help to avoid unnecessary toxic effects.

"GeneCentric Therapeutics...announced today that its PurIST^SM test is now commercially available through Tempus for clinical use. PurIST is a novel RNA-expression test that identifies patients with the classical subtype of pancreatic ductal adenocarcinoma (PDAC) who are likely to experience longer overall survival (OS) with standard-of-care (SOC) FOLFIRINOX than patients with the basal subtype of PDAC."

Funding: ZonMw (the Netherlands Organisation for Health Research and Delevopment) "Goed Gebruik Geneesmiddelen"-programma, project 848101012.Background: The first-line treatment for metastasized pancreatic ductal adenocarcinoma (PDAC) is a combination treatment with fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX). Our results indicate that the predictive value of transcriptomic subtyping can be translated into a large Dutch real-world cohort, consisting of academic and regional hospitals. Given that only half of the prospectively included patients yielded evaluable biopsies for RNA-sequencing, probably surrogate biomarkers for transcriptome-based subtyping, such as immunohistochemistry, will be more feasible in clinical practice to predict FOLFIRINOX response.

Initial data suggests worse outcomes to FOLFIRINOX (FFX) compared with gemcitabine nab-Paclitaxel (GnP) in basal tumors... Our work represents the largest known real world molecular comparison of transcriptional subtypes of PC. Differential outcomes for patients with basal tumors treated with FFX versus GnP warrants further investigation in prospective studies.

Treatments were Abraxane-Gemcitabine (n=63), PAXG (n=40), FOLFIRINOX (n=36)... Cigarette smoking seems associated with worse response to first-line FOLFIRINOX in PDAC patients. The hypothesis that this is due to molecular changes induced by smoking needs further investigation.

Background : FOLFIRINOX and gemcitabine/abraxane chemotherapy regimens are first-line treatments for pancreatic ductal adenocarcinoma (PDAC)... We found that molecular subtypes of PDAC are associated with features that can be captured from H&E WSIs using a deep learning model. Identification of patients likely to have basal-like PDAC could be used to rapidly identify patients less likely to benefit from FOLFIRINOX therapy and prompt follow-up RNA expression testing for subtype confirmation. Future work includes expansion of the study to the institution’s entire set of data and demonstration of the clinical validity of this model using FOLFIRINOX therapy response data.

"GeneCentric Therapeutic...announced today the poster presentation of further clinical validation data for PurIST^SM, a novel RNA-expression test, in collaboration with Tempus. PurIST identifies patients with the classical subtype of pancreatic ductal adenocarcinoma (PDAC) that are likely to experience longer overall survival (OS) with standard of care (SOC) FOLFIRINOX than patients with the basal subtype of PDAC. The presentation will be made at the 8th AACR Special Conference on Pancreatic Cancer in Boston, Massachusetts, which runs from September 13-16, 2022."