TEST:

Tempus xT Assay

"This study aimed to predict patient outcomes to immune checkpoint inhibitors (ICI) by developing an integrated DNA/RNA ICI biomarker. A de-identified pan-cancer cohort from the Tempus multimodal real-world database was utilized to develop and validate the Immune Profile Score (IPS) algorithm that leverages Tempus xT (DNA sequencing) and xR (RNA sequencing). The researchers found that IPS status can be used to stratify patient cohorts and prognosticate ICI-treatment response....The team analyzed real-world imaging patterns from a cohort of 4,147 advanced cancer patients treated with immune checkpoint inhibitors (ICI) across five solid tumor types....Incorporating these patterns into a microsimulation model, the team demonstrated that using the molecular biomarker in conjunction with CT imaging provided substantial cost savings and reduced inappropriate therapy compared to imaging alone, with the most benefit observed in small cell lung cancer (SCLC) treated with ICI-chemotherapy."

In our dataset, we have demonstrated several recurrent genomic events which warrant investigation, highlighting the need for further analysis. We will continue to collect data with the aim of further characterizing the complex landscape of all plasma cell disorders.

Ethics Approval Tempus AI, Inc. has been granted an IRB exemption (Advarra Pro00072742) permitting the use of de-identified clinical, molecular, and multimodal data in order to derive or capture results, insights, or discoveries.Download figure Open in new tab Download powerpoint Abstract 188 Figure 1

This approach can be used for rapid assessment of heterogeneous clonality in progenitor cell populations in the context of high-throughput screenings.Download figure Open in new tab Download powerpoint Abstract 1241 Figure 1 (A) Patient-derived tumor organoids are grown in the presence of immune cells and optional drug candidates and imaged via time-series confocal microscopy to assess growth kinetics. (B) Analytical pipeline consists of: brightfield image capture; tumor organoid segmentation; organoid bounding box cropping and background subtraction; feature extraction with a pre-trained neural network, a self-supervised neural network, and CellProfiler; and mutational prediction with each extracted feature set; and tumor organoid feature visualization demonstrating individual tumor organoids rank-ordered by the model's prediction scoreDownload figure Open in new tab Download powerpoint Abstract 1241 Figure 2 Area under the receiver operator characteristics (AUROC) curve illustrates differential predictability of gene mutation status with different representation methods within tumor organoids co-cultured with immune cells, demonstrating a trend of marked utility of human-interpretable features generated by CellProfiler relative to unsupervised and self-supervised learning systems

This table includes patients enrolled in BASECAMP-1 with germline HLA-A*02 LOH status and correlative data available. Data as of 01 June 2024

Molecular differences in CRC tumor mutation frequencies and gene expression that may underlie observed differences by race and ethnicity were identified. The association of AFR ancestry with increased KRAS mutations aligns with higher CMS3 subtype rates in NH Black patients. The increase of indeterminate CMS in Hispanic/Latino patients suggests that subtype classification methods could benefit from enhanced patient diversity.

P | "In 20 months, we prospectively screened 1720 subjects using the Tempus AWARE program, identifying 26 HLA-A*02 LOH patients at 8 sites, with 14 (54%) enrolled into BASECAMP-1. In conclusion, we developed and validated an investigational assay that detects tumor HLA LOH within an FDA-approved clinical diagnostic test, enabling HLA LOH utilization in diagnostic, prognostic, and therapeutic applications."

Importantly, co-occurrence of rare fusions and EGFR classical activating mutations in patients pre-treated with anti-EGFR therapy suggests a potential resistance mechanism and consideration of upfront, dual mutation, targeted treatment to improve outcomes. Further clinical studies are needed to validate the best treatment options for these patients with rare fusions.

Table 1. Immune cell quantification in primary and metastatic NSCLC Characteristics Lung (L) N=3,823 1 Liver (LV) N=937 1 CNS N=1,035 1 Bone (B) N=739 1 L vs. LV q -value 2 L vs. CNS q-value 2 L vs. B q-value 2 % IC of all cells 21 (13, 28) 14 (6, 21) 17 (8, 26) 13 (6, 21) 0.05 0.05 IC = immune cells 1 Median (IQR) 2 Dunn's test with FDR correction

Some atypical fusion partners were observed in white and BAA that were not observed in other races. These data emphasize the importance of testing lung cancer patients with assays that allow for unbiased fusion detection and identification of novel fusion partners across racially diverse populations to better understand racial and ethnic differences in ALK-rearranged lung cancers.

"Overall, these data suggest that MSI/dMMR CRC harboring RAS mutations are less immunogenic and appear to contain a lower tumor inflammatory profile of TIME than RASwt or BRAF V600E mutated tumors. Further analysis and validation are needed to confirm our data."

In a real-world, retrospective analysis of a cohort of advanced NSCLC patients, most oncologists utilized CGP to identify and treat patients with guideline-recommended variant matched targeted therapy, with adherence rates varying by variant. Importantly, even patients that received CGP results prior to FDA approval of novel therapies, received matched therapy once they were included in guidelines.

"Tempus AI, Inc...today announced that the Centers for Medicare & Medicaid Services (CMS) has granted Advanced Diagnostic Laboratory Test (ADLT) status for Tempus’ next-generation sequencing assay, xT CDx. xT....This CMS determination affirms that Tempus’ xT CDx meets the rigorous criteria for new ADLT status, which is reserved for novel products that provide new clinical diagnostic information that cannot be obtained any other way, or products cleared or approved by the FDA. The initial ADLT rate established by CMS is $4,500. During the nine-month period beginning July 1, 2024 and ending March 31, 2025, Tempus shall be reimbursed the established ADLT rate while it collects and submits to CMS the private payor payment amounts for xT CDx. Beginning April 1, 2025, CMS will establish a new Medicare rate based on the weighted median of private payer amounts."

Further research is warranted to elucidate how longitudinal ctDNA analysis can delineate biomarkers of response and resistance at both the mutation and ctDNA fraction levels. Understanding these dynamics could offer valuable insights into disease progression and guide personalized treatment strategies for RCC patients.

METex14 tumors exhibited differences in IO biomarkers and the somatic landscape compared to non-METex14 NSCLC tumors. Variations in immune profiles can affect immunotherapy selection in MET-altered NSCLC and require further exploration.

Patients with POLE/POLD1 mutations exhibited significant differences across immunological markers (ie, TMB, MMR, and MSI-H) and molecular co-alterations. Those with short variant mutations represented 18% of the POLE/POLD1 cohort and 0.4% of the total cohort examined. This group of patients had a median TMB of 159 mut/Mb (range 34-488), representing the ultra-hypermutated phenotype. This group of patients is important to identify given the potential for exceptional response to immune checkpoint inhibitors.

Our findings show that BRCAm is independently prognostic of metastasis in a RW, localized/locoregional, high-risk PCa population. We identify high-risk BRCAm patients as a subgroup with significantly elevated risk of developing metastasis; clinical trials with targeted therapeutic intervention may be needed to address the clinical unmet need.

Compared to PB and lung, liver and bone had immune cell infiltrates indicating a less immunogenic TIME in the overall TNBC population. Although limited by sample size, this is one of the first studies to assess the TIME across race and sites of disease. These findings are hypothesis generating and provide further rationale to better understand how the TIME across disease sites and race may alter the efficacy of ICIs in TNBC.

Marker prognostic ranking was consistent between the PORTEC-3 high risk cohort and all risk levels in RWD despite absolute RFS differences likely due to differences in baseline characteristics and outcome assessments. The consistent poor prognosis of p53abn patients, good prognosis of POLEm albeit with limited power, and moderate prognosis of NSMP and dMMR patients in RWD support use of these markers to inform treatment decisions across disease risk levels in an early EC setting.

Via comprehensive molecular characterization of UC, we observed distinct DNA alteration and tumor microenvironment patterns in UTUC and UCB. The germline results underline how T/N testing can identify patients with UTUC and/or UCB who can benefit from dedicated germline testing. Further research is warranted to elucidate the clinical implications of these findings.

This analysis shows that ctDNA profiling is complementary to tissue based NGS in RCC and can increase the detection of mutations. Concordance between ctDNA and tissue profiling increased in individuals with metastatic disease. Future research is warranted to understand how longitudinal ctDNA analysis can define biomarkers of response and resistance at the mutation and ctDNA fraction levels.

In this large, real-world cohort of pts with metastatic NSCLC, DDRmt was associated with distinct TIME patterns including high TMB, MSI-H, and modest changes in immune cell infiltrates. These findings warrant further studies to understand how DDR pathway alterations mediate changes in the TIME to inform novel combinatorial immunotherapeutic approaches in NSCLC.

"Tempus...announces the clinical launch of p-MSI, a digital pathology algorithm using H&E whole slide images that is available with the company’s xT assay for patients with prostate cancer. This offering aims to identify patients who may be more likely than the average patient with prostate cancer to have a tumor that is microsatellite instability high (MSI-H), and therefore potentially eligible for immunotherapy."

EUS-FNB with ROSE was associated with significantly more procedure time and needle passes than without ROSE but produced similar rates of specimen adequacy for genomic analysis. As such the routine utilization of ROSE may not be warranted for the evaluation of solid pancreatic lesions.

Distinct molecular characteristics including tumor immune components and genomic alterations are associated with 1L response in advanced NSCLC. Real-world data analyses provide opportunity to explore distinct mechanisms of therapy resistance and identify potential biomarkers of therapy response for further validation in clinical studies.

Here we introduce a novel sensitive and specific tumor-informed, non-bespoke approach for estimating ctDNA TF. Linearity improves with increased panel size and increased variant number. These results suggest that a tumor-informed ctDNA TF can be utilized to improve the sensitivity of existing methods for estimating tumor fraction to help in treatment decisions using Tempus' tissue and liquid comprehensive NGS genomic profiling platform.

Race/ethnicity was associated with RTK changes in both groups, with ASN and HLN having more mutations than NHW, but the associations were not significant after correcting for multiple hypotheses. There was no association of race/ethnicity and TMB .Somatic changes in RTK genes were associated with AMR genetic ancestry; however, despite the relatively large cohort size, these results are modest, suggesting there is not a large somatic mutation component contributing to differences in pancreatic cancer outcomes by ancestry.

Lastly, we identified novel positive associations between AMR and driver mutations in PIK3C3A (OR=1.12, p=0.0003) as well as small NS mutations or CNAs in the PI3K/AKT/mTOR pathway genes (OR=1.03, p=0.04). By analyzing a large, diverse real-world cohort and leveraging NGS-inferred genetic ancestry, our study confirms known associations between somatic alterations in PRAD cancer genes and race and ethnicity, while unveiling novel associations in understudied populations of potential significance for understanding disparities in disease outcomes.

A novel classifier trained on multiple orthogonal bioinformatics features can reliably distinguish CH from tumor-derived variants using only liquid biopsy data with high accuracy, including high sensitivity and high specificity.

These results suggest that PDOs may serve as a powerful tool for predicting patient response to treatment and aid the development of new therapies.

High-grade SPC are occasionally encountered and not well-characterized. Similar to their lower-grade counterparts, approximately half show NE differentiation. However, in contrast, these cases frequently have more aggressive features such as necrosis, LVI/nodal metastases and alterations in cellular proliferation pathways and tumor suppressor transcription factors.

High-grade SPC are occasionally encountered and not well-characterized. Similar to their lower-grade counterparts, approximately half show NE differentiation. However, in contrast, these cases frequently have more aggressive features such as necrosis, LVI/nodal metastases and alterations in cellular proliferation pathways and tumor suppressor transcription factors.

HC is predominantly lobular phenotype but rare cases can exhibit E-cadherin expression. With ER low+/triple-negative status and low proliferation index, HC may not be responsive to chemotherapy or endocrine therapy, yet frequently recurs or metastasizes. Targeting the PI3K pathway or AR is a potential therapeutic strategy.

Molecular and immune profiling of primary and metastatic lesions in this cervical cancer cohort revealed similar phenotypes, suggesting that predominant biologic pathways are preserved. Further interrogation of the molecular landscape across paired and serial samples is needed to better inform the development of novel therapies.

Analyzing de-identified data from over 100,000 cancer patients sequenced with the Tempus xT panel, we demonstrate that both methods outperform existing geolocation and surname-based methods, with the machine learning approach achieving high recall (range: 0.859-0.993) and precision (range: 0.932-0.981) across four mutually exclusive race and ethnicity categories. This work presents a novel pathway to enhance RWD utility in studying racial disparities in healthcare.

"Tempus...announced its participation in the National Cancer Institute’s (NCI) ComboMATCH group of precision medicine trials. The ComboMATCH trials aim to pair patients with a therapy that has the potential to manage their tumor and help assist physicians in devising more effective treatment strategies for individuals with locally advanced or advanced solid tumors. Tempus is one of the NCI-designated commercial laboratories for the initiative...Oncologists at participating ComboMATCH clinical sites can leverage their patients’ results from Tempus’ signature xT assay to determine their potential suitability for the program’s treatment trials."

This is the largest investigation of the PIK3R1 mutational landscape in breast cancer patients (n = 6,009). PIK3R1 mutations were more common in triple-negative breast cancer (~ 6%) than in HER2 + or HER2-/HR + disease (approximately 2%). While alterations in the PI3K/AKT pathway are often actionable in HER2-/HR + breast cancer, our study suggests that PIK3R1 could be an important target in TNBC as well.

P=N/A; N=50; Recruiting; Sponsor:Tempus Labs

Distinct genomic alteration patterns were found among different histologic subtypes of bladder cancer and conventional UC. Assessing the genomic landscape of bladder cancer can help identify potential ‘actionable’ targets and biomarkers, and better inform clinical trial designs. Limitations include lack of clinical data annotation, tumor heterogeneity and retrospective study nature.

Use of an RNA-based HRD signature significantly expands the fraction of patients with prostate cancer who may derive benefit from poly (ADP-ribose) polymerase inhibitors (PARPis) compared with using HRR gene mutations alone. Further studies are needed to evaluate functional HRD significance and inform future usage as a predictive biomarker for PARPi selection.

This is the largest known data set exploring the genomic and immune landscape of BTC with ARID1A, PBRM1 and BAP1 alterations. Macrophages were the dominant immune cell TME and may be a target of interest. Co-alteration profile is distinct between ARID1A- vs PBRM1- and/or BAP1-altered BTC.

HER2 amplifications were found in 10% of advanced BTC and did not represent an independent predictive factor for OS. Of clinical significance, patients with HER2-amplified BTC derive a significant benefit from anti-HER2 therapy.