TEST:

BluePrint

"Agendia®, Inc., today announced it will be presenting new data highlighting MammaPrint® and BluePrint® utility in guiding treatment decisions for patients with early-stage breast cancer. The findings will be presented in two spotlight presentations and two posters at the San Antonio Breast Cancer Symposium 2024 (SABCS), on Wednesday, December 11th and Thursday, December 12th."

P=N/A, N=50, Recruiting, Stryker Trauma and Extremities | Trial completion date: Jan 2025 --> May 2025

(early data and active trial) Who may benefit from the addition of anthracycline to their chemotherapy regimen (AC-T/TC)? Who may benefit from extended endocrine therapy?

(early data and active trial) Who may benefit from the addition of anthracycline to their chemotherapy regimen (AC-T/TC)? Who may benefit from extended endocrine therapy?

We selected 108 CLL patient samples with genetic annotation and exposed them ex-vivo to small-molecule inhibitors used clinically (ibrutinib/BTKi, duvelisib/PI3Ki, trametinib/MEKi, everolimus/mTORi, selinexor/XPO1i) or targeting key signaling pathways (compound 26/TLRi, MK2206/AKTi, nutlin-3a/MDM2i, IBET872/BETi) for 48h. In conclusion, the addition of targeted pathway perturbations to the GEP of primary CLL samples can greatly enhance the potential for molecular and functional classification of disease and subgroups. Our study provides a blueprint to use perturbed omics profiling and interaction testing to link disease drivers to pathway activation and function.

Finally, consistent with DNA hypomethylation reflecting the proliferative history of MM, the PR subtype had the most pronounced DNA hypomethylation. Notably, the PR subtype had reduced DNAm at E2F1 motifs and E2F1 exclusively bound unmethylated regions of the genome, suggesting the DNAm restricts the proliferative program of high-risk MM.

Of the 978 patients (Caucasians:81.7%; African Americans:2.58%; other races: 5.7%), the risk or genetic profile was as follows: MP: Ultra-Low = 76 (8%), Low = 176 (18%), High1 = 315 (32%), and High-2 = 411 (42%); BP: Luminal A 250 (26%), Luminal B = 250 (26%), HER2 = 228 (23%), and Basal = 250 (26%). The mean age was 58.84±13.04, the average BMI was 30.04±7.34, and the majority were postmenopausal (n = 717, 73%). The first five PCs accounted for 63.11% of the total variance of the dataset.

The trial reached the pre-specified tpCR, had met the primary end point. Neoadjuvant pyrotinib, trastuzumab and nab-paclitaxel reached a high tpCR rate, with manageable toxicity, for patients with HER2-enriched subtype of HER2-positive breast cancer. Chemotherapy can be de-escalated in patients with HER2-enriched subtype breast cancer with BluePrint intrinsic subtyping.

These data suggest that patients with MammaPrint Low Risk, cT3 tumors are unlikely to respond to NCT. These data are in alignment with long-term follow-up, level 1A evidence from MINDACT showing that patients with MammaPrint Low Risk HR+HER2- tumors may safely omit chemotherapy, regardless of nodal involvement. Intuitively, testing newer agents or neoadjuvant endocrine therapy for downstaging or proceeding to definitive surgery should be considered for genomically low-risk, cT3 cancers.

The DETERMIND study indicates that the MP/BP test is a useful tool for establishing the indication of QT in high clinical risk HR[+]/HER2[-] EBC, as well as its feasibility in the initial tru-cut biopsy. These results are consistent with the data from the MINDACT study, supporting QT de-escalation in patients with low genomic risk and good prognosis.

The FLEX trial represents a pioneering effort in integrating genomic data and clinical information on a large scale to improve outcomes and reduce disparities in EBC. Its emphasis on diversity, comprehensive data collection, and collaborative research pursuits places it at the forefront of precision medicine in EBC.

In the MINDACT trial exploratory analysis most HER2-low tumors were HR positive, Luminal A BC molecular subtype and Low MP genomic risk. However, HER2-low BC is not a uniform biological entity with an enrichment of Luminal B and High MP genomic risk in the HER2 2+ score subset. In addition, this analysis demonstrated that clinical outcome of HER2-low early BC is associated with MP genomic risk.

TIL levels are higher in early-stage HR-positive breast carcinomas with a high recurrence risk. These tumors also harbor targetable genomic alterations, suggesting that TIL measurement and genomic profiling could enhance risk stratification and identify patients who might benefit from targeted therapies. Her-2 low expression in high-risk patients provides a consideration for including novel ADC therapies in this subset of patients.

MammaPrint and BluePrint predict chemosensitivity to NCT in HR+HER2- EBC. Patients with MammaPrint H2 tumors, including Luminal B and Basal subtypes, are more likely to achieve pCR or PR to NCT, compared to UL, LR, and H1 groups. Additionally, pCR rates trended lower among LN positive disease, possibly due to the increased difficulty of clearing disease in LNs with systemic therapy.

While immune markers such as TILs and PD-L1 scores are not typically measured in HER2-positive breast cancers, this data opens up the possibility of rationally leveraging targeted therapies in this subset of immune and HER2-sensitive breast cancers, thus potentially avoiding chemotherapy in the future for this biologically selected group. This regimen holds promise as an effective, relatively non-toxic, and biologically-driven alternative to standard chemotherapy for patients with HER2- enriched subset of early breast cancer.

Among patients with high molecular-risk HR+/HER2- EBC, the MP-High2, BP-Basal-type, and ImPrint positive signatures identified a partially overlapping subset of patients who were more likely to achieve pCR in response to neoadjuvant chemotherapy +/- targeted agents or immunotherapy compared to patients with MP-High1, BP-Luminal-type, and ImPrint negative disease. I-SPY2.2 is incorporating the use of these biomarkers to molecularly define specific patient populations and optimize treatment selection.

We performed surgery, postoperative radiotherapy, and hormonal therapy in a breast cancer patient with vascular EDS without major complications.

"Agendia, Inc. today announced that it has obtained certification from the European Union (EU) In Vitro Diagnostic Medical Device Regulation (IVDR) for three products, including its MammaPrint FFPE Microarray, BluePrint FFPE Microarray, and MammaPrint and BluePrint NGS Kit. These products are classified as Class C under this regulation."

These mutations impact cancer onset age and severity, underscoring the need for targeted testing and screening. The current study enhances cancer detection, prevention, and cure strategies.

MammaPrint and BluePrint classification highlights racial disparities in the distribution of distinct High Risk molecular subtypes among HR+HER2- early BC. However, survival at 3 years was driven by molecular subtype, independent of race, after controlling for potential confounders. These data highlight the importance of tumor genomic testing to inform treatment decisions as we strive to reduce racial survival disparities among Black females with BC.

Patients with Luminal Low-Risk breast cancer had a long-term benefit from 2 years of adjuvant tamoxifen up to 20 years beyond primary diagnosis. No significant benefit was seen for Ultralow or Luminal High-Risk patients. This highlights the importance of extended follow-up to understand treatment benefit and the importance of individualized management for ER-positive patients.

The multidisciplinary breast cancer team recommended NAT with pembrolizumab, carboplatin, paclitaxel, doxorubicin, and cyclophosphamide. This case underscores the potential benefits of neoadjuvant chemoimmunotherapy for patients with ER+ErbB2- high-risk, basal-type breast cancer. The use of immunotherapy in patients with pregnancy-associated breast cancer remains to be further investigated.

Sponsored by Agendia NV

Early-stage HR-positive breast carcinomas have low TIL levels regardless of the recurrence risk, molecular subtype, and HER2- low status. These cancers are markedly enriched by HER2-low phenotype, which might have therapeutic implications due to the recently approved anti-HER2 antibody-drug conjugate.

P2 | N=28 | Recruiting | Sponsor: University of Illinois at Chicago | Not yet recruiting ➔ Recruiting

P2 | N=28 | Not yet recruiting | Sponsor: University of Illinois at Chicago

P=Obs | N=25,000 | FLEX (NCT03053193) | Sponsor: Agendia | "Agendia, Inc. today announced it will present new data on the 3-year outcome of patients with hormone receptor-positive (HR+), HER2-negative early-stage breast cancer when treated with two different chemotherapy regimens at the 2024 Annual American Society of Clinical Oncology (ASCO) Meeting, taking place in Chicago, IL. on May 31st, 2024....Results showed that patients with MammaPrint H1 Luminal B-Type tumors demonstrated similar 3-year outcomes when treated with either TC (97.1%) or AC-T (95.3%), suggesting that patients who are classified as H1 may be able to avoid the toxicity of an anthracycline. However, patients with MammaPrint H2 Luminal B-Type tumors demonstrated a significantly higher relapse-free survival when treated with AC-T (97.7%) than with TC alone (86.4%). These findings indicate that MammaPrint H2 tumors benefit from the addition of an anthracycline to their adjuvant chemotherapy regimen."

These findings increase our understanding of this rare, but clinically important HER2 category. Large-scale prospective randomized studies are needed to further evaluate the role of perioperative HER2-targeted therapy in this patient population.

"Agendia, Inc., announced today that new data on its comprehensive genomic tests will be presented at the American Society of Clinical Oncology Annual Meeting (ASCO), taking place May 31st – June 4th, 2024, in Chicago, Illinois....The two abstracts that have been selected by ASCO for oral discussion will 1) feature an investigation of underlying biology that mediates immune therapy response and, 2) will provide an evaluation of the MammaPrint Index and 3-year recurrence-free interval in patients treated with CT, with and without anthracycline. Both presentations utilize whole transcriptome data from the prospective, observational real-word evidence FLEX Study (NCT03053193)."

Our study showed a high rate of discordance between clinical and genomic risk, a rate of 49% between clinical high-risk and genomic high-risk patients, highlighting the importance of these assays in the decision-making of breast cancer patients. This represents the first cohort to evaluate MammaPrint+BluePrint in a Latin American population. A noteworthy result was identifying a significant proportion of our cohort as low-risk through genomic assay, sparing them from the toxic effects and expenses associated with chemotherapy.

Here, the association of MP index and 3-year (yr) Recurrence-Free Interval (RFI) was evaluated in pts with HR+HER2-, genomically High Risk Luminal B-Type EBC treated with taxane and cyclophosphamide (TC) vs anthracycline + TC (AC-T)... These data show that among pts with Luminal B-Type tumors, MP H2 have significantly worse 3-yr RFI than pts with MP H1 tumors when treated with TC. This further supports ongoing research demonstrating the significant benefits of anthracycline-based CT for treating H2 Luminal B-Type tumors. Conversely, MP H1 tumors do not appear to benefit from the addition of anthracycline to CT regimen.

High rates of discordances between BP and clinical factors/IHC were identified in this Black patient population. Reclassification sometimes affected treatment decisions, leading to favorable results such as pCR after NAC. Our findings suggest that genomic profiling at time of CNB could be beneficial for Black patients, as treatment decisions based on reclassifications could potentially improve outcomes.

"Agendia®, Inc...announced...that the company’s 80-gene molecular subtyping assay, BluePrint®, is now included in the latest version of German Gynecological Oncology Group (AGO) guidelines. The assay was added to the list of predictive factors for neoadjuvant chemotherapy decision making."

P=N/A, N=50, Recruiting, Stryker Trauma GmbH | Not yet recruiting --> Recruiting

These findings are consistent with the poor clinical outcomes previously reported for PPBC. Increased frequency of MP High 2 tumors and immune biology indicate that PPBC might benefit from adding immunotherapy, to be explored in future trials.

Supported by Agendia. Overview: During this symposium, Jaime Alberty MD, FACS (Breast Surgeon) and William Audeh MD, MS (Medical Oncologist & Chief Medical Officer at Agendia) will discuss the latest data and share case studies leveraging MammaPrint® + BluePrint® gene expression profiling to optimize treatment plans for patients with Early-Stage ER+ Breast Cancer.

P=Obs | N=25,000 | FLEX (NCT03053193) | Sponsor: Agendia | "Agendia, Inc., announced today it will share new data from the ongoing prospective, observational FLEX Trial (NCT03053193) in two poster presentations at the 41st Annual Miami Breast Cancer Conference (MBCC), taking place March 7 – 10th, 2024...The first poster....Results showed that patients with MP High 2 tumors, including Luminal B and Basal subtypes, are more likely to achieve a pCR in response to AC-T, while the addition of anthracycline to the therapy regimen does not appear to improve pCR rates for patients with MP High 1, Luminal B-type tumors."

Chemotherapy-free neoadjuvant regimen with DTP in HER2-enriched EBC showed high pathologic response rates comparable to that with chemotherapy. This DTP regimen may provide an effective, relatively non-toxic, and biologically driven alternative to standard of care chemotherapy in this HER2-enriched subset of EBC.

P2 | N=67 | Active, not recruiting | Sponsor: City of Hope Medical Center | Trial completion date: Dec 2023 ➔ Dec 2024

Sponsored by BluePrint Medicines

In this study, we identified the clinical and genetic characteristics of ER + /PR- breast cancer patients in China. Distinct PR statuses indicated different biological processes of ER + breast cancer and survival outcomes. Future treatment strategies may need to be tailored for ER + /PR- patients.

These data demonstrate MammaPrint and BluePrint utility to predict the likelihood of achieving pCR after NCT in HR+HER2- ESBC. Although both MP High Risk groups exhibit chemosensitivity, High 2 tumors have higher chemosensitivity than High 1 tumors. MP High 2 status can be utilized to identify ER+ patients who are the most likely to experience pathologic downstaging and pCR after NCT.