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MSK-ACCESS

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.

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.

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.

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.

Recent preclinical studies further suggest that onapristone adds to inhibition of cell proliferation when combined with CDK4/6 inhibitors and fulvestrant. The trial is currently open to enrollment at MSKCC. Contact Information: Dragoj@mskcc.org; Jhaverik@mskcc.org

Patients will receive a baseline blood draw, a BBB opening treatment with the Cordance device, followed by a blood draw after the treatment. Liquid biopsy tests to be examined include the MSK ACCESS test and tumor-informed ddPCR MRD test.

The somatic co-mutational spectrum appears typical of PC, with notable findings of ARID1A gene variant enrichment (20%) and slightly higher median TMB, noted. Ongoing studies are establishing the role of direct KRASG12C inhibition with single/combination strategies.

cfDNA-based NGS profiling yielded low detection rates in this metastatic ccRCC cohort. Concordance with tumor profiling was low, even for truncal mutations such as VHL, and some findings in peripheral blood may represent clonal hematopoiesis. Routine cfDNA panel testing is not supported, and its application in biomarker efforts must account for these limitations.

"Seventeen of the 25 patients with stage III disease received durvalumab... We demonstrate the feasibility of prospective profiling with liquid biopsy to identify genomic markers of RT response including somatic mutations associated with RT sensitivity and resistance. This data may inform future evaluations of personalized, genomically-guided thoracic RT for lung cancer."

In this small cohort, detectable ctDNA is associated with the presence of active/progressing metastatic uveal melanoma. Detectible ctDNA in patients without known metastatic disease may herald the development of radiographically evident metastasis.

Patients with recurrent/persistent MSI-H/dMMR/hypermutated EC with measurable disease and ≥1 prior lines of cytotoxic therapy were treated from 06/2018-01/2022 with nivolumab until progression of disease (PD) or unacceptable toxicity... In patients with advanced hypermutated ECs, cfDNA sequencing can be used to accurately detect MSI status. Early changes in ctDNA fraction may be associated with durable response to ICI or may anticipate radiological progression. Future studies may use ctDNA to assess mechanisms of ICI resistance and offer opportunities for adaptive therapy intervention.

Circulating cfDNA genotyping with MSK-ACCESS identifies previously reported HCC tumor genomic profiles and revealed tumor-associated mutations in 92.5% of plasma samples. Ongoing efforts will explore predictive and prognostic implications of NGS at different HCC stages as well as kinetics of treatment response.

Neratinib is tolerable with modest antitumor activity in patients with BTC harboring HER2 mutations. Although the primary endpoint was met, future studies should evaluate rational combinations to augment and/or prolong responses.

Pts with mUC treated with erda demonstrated on-tx acquisition of ctDNA alts of FGFR2/3 and TP53 and activating alts downstream or parallel to FGFR signaling. Most pts with TP53 alts in baseline ctDNA were refractory to erda. Acquired FGFR2/3 alts on erda may drive resistance through interference with drug-target binding.

In sum, our analysis of patient-matched primary and metastatic urothelial carcinomas revealed a high degree of lesion-to-lesion genomic heterogeneity that may be a barrier to precision oncology approaches for this disease. Our data also provide a rationale for the use of cell-free DNA sequencing to guide targeted therapy selection in patients with metastatic urothelial cancer.

Results were highly concordant in both inter- and intra-assay reproducibility studies.Overall, these data indicate that MSK-ACCESS Heme is a robust cfDNA-based assay that can be used to detect variants at low frequency with high reproducibility. Future work sequencing additional samples will be performed to further assess the performance of the panel.

Recent preclinical studies further suggest that onapristone adds to inhibition of cell proliferation when combined with CDK4/6 inhibitors and fulvestrant. We will allot for 5 additional patients to account for inevaluability during the dose escalation and expansion portions of the trial. The trial will be open to enrollment at MSKCC in July 2021.

"The median age was 70 (IQR: 62-78) years, 75% were male, and 50% received 4 cycles of neoadjuvant gemcitabine and cisplatin. MSK-ACCESS can detect cfDNA in ~75% of patients with localized bladder cancer. ACCESS appears specific for muscle-invasive disease. The negative predictive value was 60%."

cfDNA tumor fraction can inform the interpretation of negative cfDNA results and guide the selection of subsequent sequencing platforms that are most likely to identify clinically-relevant genomic alterations.

Conclusions MRD was identified in 18% of resected MMRd tumors using ctDNA analysis, suggesting this to be a feasible tumor agnostic approach to test the efficacy of CPB in pts at high risk for recurrence. Future studies will assess the impact of CPB in MRD-positive MMRd tumors.

This large study highlights the challenges and complexities of using cfDNA to profile advanced renal cell carcinoma. Mutation detection in cfDNA was enhanced using prior knowledge from tumor tissue profiling and crossgenotyping methods. The use of patient-matched samples greatly increased our ability to detect and filter patient SNPs and/or CH mutations from our tumor calls and demonstrates the importance of these controls in genomic profiling.