TEST:

MSK-ACCESS

Verification results of the decentralized MSK-ACCESS powered with SOPHiA DDM solution demonstrate a high concordance to the single-site test developed by MSK. This provides laboratories with a cfDNA solution that interrogates frequently mutated genomic regions in cancer and moderates the risk of incorrectly reporting germline and CH alterations through the inclusion of matched WBC testing.

Conclusion In this large cohort of MBC pts, ctDNA detection and levels emerged as strong prognostic indicators for OS, independently from disease burden. Our data suggest that ctDNA levels can provide valuable insight into tumor biology as well as disease burden and may be utilized for early prognostication in MBC.

These findings were consistent with those reported for SUMMIT hormone receptor-positive (HR+) HER2-mutant mBC cohorts, in which patients treated with N or N + fulvestrant (N+F) experienced promising clinical responses but shorter DOR. Although limited by small numbers, addition of T to N in patients with HER2-mutant mTNBC, despite deepening and prolonging response, did not appear to preclude eventual emergence of either on-pathway (ERBB3) or off-pathway (KRAS, TP53) mutations. In contrast to observations in N+F+T-treated patients with HR+, HER2-mutant disease, no additional HER2 alterations were detected upon progression in N+T-treated patients with mTNBC in this small dataset. Future investigations may evaluate clinical utility of sequencing therapies targeted to mutations acquired in response to N-based therapy in patients with HER2-mutant mTNBC.

Methods Patients with MSI-H/dMMR/hypermutated EC and ≥1 prior cytotoxic lines received nivolumab until progression/toxicity...Conclusion/Implications In patients with advanced MSI-H/dMMR/hypermutated EC, changes in ctDNA are detected as early as 2 weeks after ICI initiation, can anticipate radiologic progression/response, and can monitor durable responders. Future studies may use ctDNA to assess mechanisms of ICI resistance and offer adaptive therapy intervention.

"SOPHiA GENETICS...announced that the company is joining the European Liquid Biopsy Society (ELBS), a prestigious network consisting of partners from academia and industry with the common goal of making liquid biopsy tests part of the routine standard of care...The ELBS primarily focuses on liquid biopsy testing for cancer, which aligns with the work that SOPHiA GENETICS has done to increase access to this sophisticated testing. SOPHiA GENETICS decentralized MSK-ACCESS®, the highly validated ctDNA assay developed by Memorial Sloan Kettering Cancer Center (MSK), so customers in Europe and worldwide have access to a best-in-class liquid biopsy solution."

"SOPHiA GENETICS...announced a new milestone in the global introduction of the liquid biopsy test MSK-ACCESS powered with SOPHiA DDM, first announced in October 2023. Under a definitive partnership agreement with AstraZeneca...SOPHiA GENETICS will accelerate the deployment of MSK-ACCESS powered with SOPHiA DDM to 20 locations worldwide over the next 12 months...The testing works by isolating cell-free DNA (cfDNA) from blood plasma to uncover circulating tumor DNA (ctDNA)...The partnership with AstraZeneca will further catalyze the adoption of MSK-ACCESS powered with SOPHiA DDM....As more hospitals and labs go into routine, SOPHiA GENETICS and AstraZeneca, in collaboration with leading cancer institutes within the SOPHiA GENETICS community, will generate a vast set of real-world data from patients around the world with a variety of cancers. This data set has the potential to generate unique insights towards advancing cancer research and drug development."

Our findings highlight the potential for cfDNA assays to detect mosaic RB1 variants with VAFs as low as 1%. Mosaicism for RB1 should be examined for any RB patient undergoing cfDNA testing where an RB1 variant persists despite no clinical evidence of disease. Enhanced detection of mosaicism in RB1 can allow for optimal counseling, treatment, and surveillance.

Chemoimmunotherapy remains a major treatment option for metastatic HER2-mutant NSCLC. ctDNA can rapidly detect HER2 and co-mutations, and it has the potential to guide and monitor optimal first-line therapy. As a negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies.

"SOPHiA GENETICS...announced...that OncoHelix...will implement MSK-ACCESS® powered with SOPHiA DDM™. The organization, which currently uses the SOPHiA DDM™ Platform for myeloid testing, will use the new liquid biopsy solution to advance its oncology testing capabilities. OncoHelix will be live on MSK-ACCESS® powered with SOPHiA DDM™ later this summer."

In newly diagnosed advanced GIST, ctDNA detection rate of the GIST genotype was low and inversely correlated with duration of rx exposure. However, ctDNA responses proceed radiographic responses, which may be further exploited for non-invasive monitoring of rx response and emerging therapeutic resistance mutations.

Considering the recent approval of capivasertib for HR+/HER2- metastatic breast cancer (MBC) harboring PI3K-AKT pathway alts based on tissue NGS, we assessed the concordance of tissue and ctDNA NGS for PIK3CA, AKT1, PTEN as well as ESR1. We identified 367 HR+/HER2- MBC pts treated at MSK with tissue NGS by MSK-IMPACT within 60 days of ctDNA NGS by either Guardant360 or MSK-ACCESS, without intervening therapy... Tissue-ctDNA concordance for the detection of any oncogenic alteration was high for PIK3CA, AKT1, moderate for ESR1, and low for PTEN. More alts were detected in ctDNA for ESR1 and in tissue for PTEN, reflecting acquired ESR1 alts after estrogen deprivation and the current lack of ctDNA assay PTEN copy number loss detection. Additional correlative analyses (e.g.

"SOPHiA GENETICS...announced...that the IUCT-Oncopole (called 'Oncopole'), a comprehensive cancer center in Toulouse, France, has expanded its research and testing abilities with the implementation of MSK-ACCESS® powered with SOPHiA DDM™. Clinicians at Oncopole will use the liquid biopsy testing capabilities to conduct non-invasive cancer genomic profiling and monitoring for patients."

P2; Serial cfDNA monitoring may complement radiographic assessments as determinants of response and resistance to entrectinib in ROS1 fusion-positive lung cancers in addition to detecting putative resistance mechanisms on progression.

Sponsored by SOPHiA GENETICS

"SOPHiA GENETICS...announced that Nigeria-based Syndicate Bio has signed on to implement MSK-ACCESS® powered with SOPHiA DDM™. Syndicate Bio is the first lab in Africa to adopt the MSK-ACCESS® assay via the SOPHiA DDM™ Platform, and the first company to make comprehensive genomic profiling and liquid biopsy widely available to patients throughout the entire continent. The implementation of this new technology will further existing work from SOPHiA GENETICS, Memorial Sloan Kettering Cancer Center (MSK), and Syndicate Bio to advance health equity on a global scale."

The results demonstrate that the decentralized "MSK-ACCESS powered with SOPHiA DDM" solution exhibits a high degree of agreement to the results achieved by MSK. Further studies will be conducted to expand the analytical performance evaluation.

Addition of trastuzumab (T) to N + fulvestrant (F) in HR+, HER2-negative, HER2-mutant mBC revealed increased efficacy compared to N+F [Jhaveri et al...Loperamide prophylaxis was mandatory during the first two cycles... Treatment with either N and/or N+T yielded promising clinical efficacy and has been included in recent NCCN guidelines for HER2-mutant, triple-negative mBC. Molecular mechanisms of intrinsic or acquired sensitivity/resistance per genomic analysis will be reported.

By combining MSK’s clinical expertise in cancer genomics and the predictive algorithms of the SOPHiA DDMTM Platform, we aim to expand access to precision cancer analysis capabilities worldwide. Join our expert speakers to gain insights into the clinical utility of liquid biopsy at MSK and explore the analytical performance data of MSK-ACCESS® powered with SOPHiA DDMTM - a decentralized application

"SOPHiA GENETICS...announced an expanded suite of solutions under SOPHiA DDM™ for Liquid Biopsy. The range of solutions, including MSK-ACCESS® powered with SOPHiA DDM™ and custom solutions, will help progress oncology research and tumor mutation profiling. The rollout of SOPHiA GENETICS' liquid biopsy capabilities demonstrates the company's commitment to developing advanced solutions that empower timely, critical decision-making and improve health outcomes."

Our findings highlight the utility of cfDNA with MSK ACCESS as a complimentary tool for molecular characterization and potential prognostication in patients with EG cancer. >

For patients on genomically-driven targeted therapy and RT combination trials, alterations detected using plasma ctDNA, especially PIK3CA, may be used to rapidly assess eligibility. Serial ctDNA collection may serve as a potential response biomarker with further validation.

"SOPHiA GENETICS...announced that BioReference® Health, LLC...will implement SOPHiA GENETICS’ technology and add MSK-ACCESS® liquid biopsy to its test suite. With the implementation of SOPHiA GENETICS, BioReference will be the first laboratory globally to adopt MSK-ACCESS® powered with SOPHiA DDM™. The offering will be commercially available for ordering by healthcare providers through BioReference, and its specialty division, GenPath® Oncology in 2024."

P2; Trial completion date: Nov 2024 --> Nov 2025 | Trial primary completion date: Nov 2024 --> Nov 2025

Conclusion In patients with cancer, ctDNA and cfDNA are independent biomarkers for VTE. Risk models incorporating liquid biopsy data are feasible in academic or community settings and, if prospectively validated, would provide a means of VTE risk stratification at scale.

"SOPHiA GENETICS...announced a collaboration with Memorial Sloan Kettering Cancer Center (MSK), a top cancer treatment and research institution, and AstraZeneca...to bring high quality, comprehensive cancer testing to a global scale. With this collaboration, the three leading organizations will further their shared goal to advance health equity on a global scale by providing inclusive access to comprehensive cancer testing worldwide....The partnership will provide MSK's proprietary liquid biopsy and solid tumor cancer tests – MSK-ACCESS^® and MSK-IMPACT^® – to organizations via the decentralized, technology-agnostic SOPHiA DDM™ Platform. This offering will be rapidly deployed by SOPHiA GENETICS with support from AstraZeneca's global footprint."

"Using an institutional assay, the presence of baseline cell-free ctDNA appeared prognostic in patients with unresectable, locally advanced NSCLC treated with definitive chemoradiation. We also detected driver alterations and potential markers of radiation resistance and response using ctDNA testing. Prospective cell-free ctDNA profiling may offer pathways to therapy personalization among patients with locally advanced unresectable lung cancer."

By combining MSK's clinical expertise in cancer genomics, the predictive algorithms of SOPHiA DDM™, and the power of the global SOPHiA GENETICS network, experts hope to expand access to precision cancer analysis capabilities worldwide. Hear from Michael Berger, PhD (Co-director, Marie-Josée & Henry R. Kravis Center for Molecular Oncology, MSK) about how MSK-ACCESS® and MSK-IMPACT® powered with SOPHiA DDM™ will raise the bar for collective intelligence in cancer research.

Off-target mechanisms of resistance appeared to be enriched in rapid and early progressors vs late progressors (75% vs 51% vs 25%, p=0.3). Conclusions RET fusion+ NSCLCs that progressed on selpercatinib prior to two years, an approximation of the drug's median PFS, were enriched for select co-occurring alterations (e.g., TP53, KEAP1, and ARID1A mutations) in pre-tx samples and off-target resistance in post-PD samples.

"The IDH1/IDH2 cartridge-based assay for the Idylla system allows ultra-rapid, sensitive, and robust screening for recurrent mutations at residues R132 in IDH1 and R140 or R172 in IDH2. The system provides reliable analysis of both extracted and pre- extraction tumor tissue from numerous sources beyond FFPE, including direct blood and bone marrow samples. It markedly simplifies the workflows in the lab and enables rapid treatment decisions."

The analytical validation results demonstrate that MSK-ACCESS Heme is a robust and reliable tool that sensitively and accurately detects clinically relevant alterations in hematological malignancies. Further work will focus on confirming the clinical utility of this assay.

P1b; N=28 --> 0 | Trial completion date: Sep 2023 --> Apr 2023 | Recruiting --> Withdrawn | Trial primary completion date: Sep 2023 --> Apr 2023

55% (17/31) received chemoimmunotherapy with pembrolizumab as the first-line treatment...Additionally, 19% of patients (6/31) received a HER2-targeted antibody-drug conjugates (ADC) as first-line treatment with a median TTD of 6 months (95% CI 2-10), including 5 with T-DM1 and one who received first-line T-DXd treatment with a TTD of 9 months... Baseline plasma ctDNA has the potential to guide first-line targeted therapy for patients with HER2-mutant NSCLC. As an independent negative prognostic biomarker, detectable ctDNA at baseline would need to be taken into account for patient selection in future studies to avoid underestimating the effects of therapy.

In this updated analysis, now with long-term follow-up, the efficacy of adaptively dosed nivo + ipi resembles that of historical data for standard dose nivo + ipi. Baseline IL-6 and on-treatment changes in ctDNA warrant further prospective study as biomarkers of response to ipi + nivo. Clinical trial information: NCT03122522.

A wide variety of adult and pediatric solid tumors harbored de novo BRAF fusions. Complementary RNA sequencing optimized fusion identification in many cases. Multiple novel fusion partners were found.

ctDNA detection rates are high (89%) in pts with untreated stage IV PC, with high concordance between ctDNA and tissue-based NGS (87% - 95%). In untreated stage I-III PC, detection and concordance rates are lower (<50%). Detection rates are associated with disease burden, site of metastasis, CA 19-9/CEA levels.

However, alterations along the MAPK, PI3K, WNT, and TGF-β pathways, which are associated with trastuzumab resistance and poor survival, were detected with similar frequency on both platforms (40 v 32%, p=0.77)... Our findings in this large prospective analysis highlight the utility of cfDNA with MSK ACCESS as a complimentary tool for molecular characterization in patients with EG cancer. cfDNA in EG cancer. >*Statistically significant difference.

NAC regimens included gemcitabine and cisplatin alone (78%) or with paclitaxel (22%). Clearance of ctDNA post-NAC correlated with pathologic complete response. Approximately 70% of pts had ctDNA clearance on NAC. All pts with residual disease at RC had detectable ctDNA post-NAC.

Learn how to unlock the platform's potential to identify unmet needs, accelerate precision medicine development, and improve patient access to new therapies by securely sharing knowledge on a global scale. Discover how SOPHiA DDM™ continues to drive and accelerate the adoption of homologous recombination deficiency (HRD) analysis and our decentralized approach to MSK-ACCESS.

"Sophia Genetics said...that it has entered into a collaboration with New York's Memorial Sloan Kettering Cancer Center to combine predictive algorithms in a quest to offer new testing and analytical capabilities to cancer researchers and clinicians worldwide...Sophia will help the cancer center commercialize its MSK-ACCESS clinical liquid biopsy assay. Sophia said that the test will be the first circulating tumor DNA panel to be integrated with the company's flagship DDM analytics platform."

NAC regimens included gemcitabine and cisplatin alone (78%) or with paclitaxel (22%). Clearance of ctDNA post-NAC correlated with pathologic complete response. Approximately 70% of pts had ctDNA clearance on NAC. All pts with residual disease at RC had detectable ctDNA post-NAC.

P2; N=25; Recruiting; Sponsor:Memorial Sloan Kettering Cancer Center

These data demonstrate that the MSK-ACCESS HEME assay is a robust and reliable tool for detecting and reporting alterations in hematological malignancies with high accuracy and sensitivity. Once approved by the New York State Department of Health, this assay will be employed to prospectively monitor patients with hematological diseases in clinical setting.