On May 29, 2020 Myriad Genetics, Inc. (NASDAQ: MYGN), a leader in molecular diagnostics and precision medicine, reported the presentation of two new studies at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting demonstrating the ability of Myriad’s riskScore test to provide personalized breast cancer risk information that allows patients and physicians to make better informed clinical treatment decisions (Press release, Myriad Genetics, MAY 29, 2020, View Source [SID1234561736]).

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"We are excited to further demonstrate Myriad’s commitment to providing the best possible risk assessment tools to patients through innovation," said Nicole Lambert, president of Myriad Oncology, Myriad Women’s Health and Myriad International. "The validation data we are presenting at ASCO (Free ASCO Whitepaper) this year will support a broader launch of riskScore to even more women in the coming year with more personalized information and the unique ability to modify carrier risk through a clinically validated tool."

Summaries of the studies are below. Follow Myriad on Twitter via @myriadgenetics and keep up to date with ASCO (Free ASCO Whitepaper) meeting news and updates by using the #ASCO20 hashtag.

riskScore Presentations at 2020 ASCO (Free ASCO Whitepaper):

Title: Comprehensive breast cancer (BC) risk assessment for CHEK2 carriers incorporating a polygenic risk score (PRS) and the Tyrer-Cuzick (TC) model
Presenter: Mark E. Robson, MD, Memorial Sloan Kettering Cancer Center
Location: View Source

In this study, 358,471 women with hereditary cancer risk who were tested with a multigene panel were assessed to find 4,331 women who were carriers of deleterious CHEK2 mutations. These patients were used to develop a mathematical model to assess risk status using family history information and Myriad’s riskScore test. This model was then validated in an independent cohort of 459 women. In CHEK2 pathogenic variant carriers, a significant correlation was detected of CHEK2 status with family history (FH) (p=4.1 × 10-17) and of polygenic risk scores with FH among CHEK2 carriers (p=1.7× 10-5). Among the patients in the validation cohort, 24.0% of CHEK2 carriers were categorized as low risk (<20%), and 62.6% were categorized as moderate risk (20-50%). For 13.4% of CHEK2 carriers, risk estimation incorporating PRS and TC generated BC risks of greater than 50%, consistent with genes recognized as highly penetrant.

To view Graph 1: Precision Breast Cancer Risk Categorization of CHEK2 Carriers, please visit the following link:
View Source

Title: Performance of the IBIS/Tyrer-Cuzick (TC) Model by Race/Ethnicity in the Women’s Health Initiative
Presenter: Allison W. Kurian, M.D., M.Sc, Stanford University
Location: View Source

In this study, 91,893 women of differing racial identities with no personal history of breast cancer were followed for a median of 18.9 years to assess incidence of breast cancer. 6,836 new cases of breast cancer were diagnosed among the women. The Tyrer-Cuzick model was used to assess risk of breast cancer and then actual cases of breast cancer were compared to expected cases based upon the Tyrer-Cuzick risk assessment. The study found that the Tyrer-Cuzick model was an accurate predictor of breast cancer risk among various ethnicities except for Hispanic women where it overestimated breast cancer risk (ratio of observed versus expected cases overall was 0.95).

About riskScore
riskScore is a new clinically validated personalized medicine tool that enhances Myriad’s myRisk Hereditary Cancer test. riskScore helps to further predict a women’s lifetime risk of developing breast cancer using clinical risk factors and genetic-markers throughout the genome. The test incorporates data from more than 80 single nucleotide polymorphisms identified through 20 years of genome wide association studies in breast cancer and was validated in our laboratory to predict breast cancer risk in women of European descent. This data is then combined with a best-in-class family and personal history algorithm, the Tyrer-Cuzick model, to provide every patient with individualized breast cancer risk.

About Myriad myRisk Hereditary Cancer
The Myriad myRisk Hereditary Cancer test uses an extensive number of sophisticated technologies and proprietary algorithms to evaluate 35 clinically significant genes associated with eight hereditary cancer sites including: breast, colon, ovarian, endometrial, pancreatic, prostate and gastric cancers and melanoma.

On May 29, 2020 Isofol Medical AB’s (publ) (Nasdaq First North Premier Growth Market: ISOFOL) ("Isofol" or the "Company"), reported that it has been informed by Professor Bengt Gustavsson – founder and largest owner of Isofol – that Professor Gustavsson has initiated that all the subscription rights held by Biofol AB (an affiliated company to Professor Gustavsson), obtained in connection with the fully guaranteed preferential rights issue of approximately SEK 150 million, has been purchased by a consortium of investors (Press release, Isofol Medical, MAY 29, 2020, View Source [SID1234561578]).

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The consortium of investors has committed to Professor Gustavsson that they will subscribe for new shares in the rights issue by utilizing the purchased subscription rights.

Furthermore, Isofol has been informed by Professor Gustavsson that he intends to subscribe for new shares in the rights issue by utilizing the subscription rights Professor Gustavsson holds privately.

On May 29, 2020 EORTC reported that the long-term results of the MINDACT (EORTC 10041/BIG3-04) study were presented today in the ASCO (Free ASCO Whitepaper) virtual meeting (Press release, EORTC, MAY 29, 2020, View Source [SID1234558776]). MINDACT tests the 70-gene signature MammaPrint to help identifying breast cancer patients who would do not need adjuvant chemotherapy . In 2016, the results of the primary endpoint (distant metastasis free survival (DMFS)) at 5 years median follow up were presented . Dr Fatima Cardoso, the principle investigator of the study, presented the updated results with 8.7 years of median follow-up, with more than 90% of patients followed for at least 5 years. 6693 patients were enrolled in the randomised MINDACT study between 2007-2011. The DMFS was assessed at 5 years for 644 clinical high and genomic low risk patients who were randomised to follow the genomic risk assessment and received no chemotherapy. In addition, a secondary analysis was conducted to evaluate DMFS and overall survival in the same population of clinical high and genomic low population depending on whether chemotherapy was administered or not.

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The present analysis confirms that MINDACT is a positive de-escalation study, as the primary DMFS endpoint at 5 years is continually met in clinical high and genomic low risk patients who receive no chemotherapy. The outcome of the "intention to treat" population are shown in the table below.

At 8 years, the estimated DMFS gain for chemotherapy administration in Clinical-High/Genomic-Low is 2.6% and must be balanced with the treatment’s harmful side effects.

A subgroup analyses was performed regarding the effect of chemotherapy per age group. This analysis showed that: a) omitting chemotherapy in Clinical-High/Genomic-Low postmenopausal women continues to be safe, (DMFS gain 0.2% ± 2.3%), and a fully preserved performance of MammaPrint to forego adjuvant chemotherapy is demonstrated; b) in premenopausal women the difference seen might be clinically relevant (DMFS gain 5% ± 2.8%); importantly, this effect may possibly be related to chemotherapy-induced ovarian function suppression.

"The present analysis clearly proves that chemotherapy can safely be avoided for postmenopausal women, classified as high risk of relapse by traditional clinico-pathological factors, but with a MammaPrint test of low risk, confirming the clinical utility of this genomic test, " said Dr Fatima Cardoso, Principal Investigator of the Study and Director of the Breast Unit at the Champalimaud Clinical Centre, Lisbon, Portugal.

Research Funding:
MINDACT was supported by grants from the European Commission Framework Programme VI (FP6-LSHC-CT-2004-503426, "TRANSBIG Network of Excellence"), the Breast Cancer Research Foundation, the U.S. National Cancer Institute, the European Breast Cancer Council-, Pharmaceutical/Biotech Company, U.S. National Institutes of Health

Session Type: Oral Abstract Session
Session Title: Breast Cancer—Local/Regional/Adjuvant
Track: Breast Cancer—Local/Regional/Adjuvant
Subtrack: Adjuvant Therapy
Abstract #: 506
Clinical Trial Registry Number: NCT00433589
Citation: J Clin Oncol 38: 2020 (suppl; abstr 506)
DOI: 10.1200/JCO.2020.38.15_suppl.506
Research support: Funding

MINDACT was supported by grants from the European Commission Framework Programme VI (FP6-LSHC-CT-2004-503426, "TRANSBIG Network of Excellence"), the Breast Cancer Research Foundation, Novartis, F. Hoffman La Roche, Sanofi-Aventis, Eli Lilly, Veridex, the U.S. National Cancer Institute, the European Breast Cancer Council-Breast Cancer Working Group (BCWG grant for the MINDACT biobank), the Jacqueline Seroussi Memorial Foundation (2006 JSMF award), Prix Mois du Cancer du Sein (2004 award), Susan G. Komen for the Cure (SG05-0922-02), Fondation Belge Contre le Cancer (SCIE 2005-27), Dutch Cancer Society (KWF), The Netherlands Genomics Initiative – Cancer Genomics Centre (2008-2012), Association Le Cancer du Sein, Parlons-en!, the Brussels Breast Cancer Walk-Run and the American Women’s Club of Brussels, NIF Trust, German Cancer Aid, the Grant Simpson Trust and Cancer Research UK, La Ligue Nationale Contre Le Cancer. This trial was also supported by the EORTC Cancer Research Fund. Whole genome analysis was provided in kind by Agendia.

Role of the funding sources

The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Acknowledgments

We are grateful to all patients and families who participated in this study.

We are grateful to the European Commission Sixth Framework Programme (FP6-LSHC-CT-2004-503426), the European Community Seventh Framework Programme (HEALTH-F2-2009-223175 to the Collaborative Oncological Gene-environment Study), the Breast International Group (BIG) AISBL, F. Hoffmann-La Roche, Novartis, Sanofi-Aventis, for supporting this independent EORTC Study.

On May 29, 2020, Blueprint Medicines Corporation Presented the Corporate Presentation (Press release, Blueprint Medicines, MAY 29, 2020, View Source [SID1234558775]).

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On May 29, 2020 The University of Texas MD Anderson Cancer Center reported that results from a Phase I clinical trial led by researchers the adoptive T-cell therapy ADP-A2M4, which is engineered to express a T-cell receptor (TCR) directed against the MAGE-A4 cancer antigen, achieved responses in patients with multiple solid tumor types, including #102synovial sarcoma, head and neck cancer and lung cancer (Press release, MD Anderson, MAY 29, 2020, View Source [SID1234558773]).

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Among 38 patients treated on the trial, the ADP-A2M4 T cells resulted in overall response (OR), or tumor shrinkage, in 9 patients (23.7%) and stable disease in 18 patients (47.4%). Trial data were shared in an oral presentation at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting by principal investigator David Hong, M.D., professor of Investigational Cancer Therapeutics.

"Thus far, we haven’t seen strong responses in treating solid tumors with available cellular therapies, in large part because antigens expressed are not restricted to the tumors," said Hong. "In this trial, I’ve been encouraged to see durable responses in several patients, and the results suggest there is potential for this emerging TCR-based technology for treating solid tumors."

Adoptive cellular therapy is a form of immunotherapy that modifies immune cells to be more effective in mounting an immune response against cancer. For ADP-A2M4, T cells are isolated from patients and engineered to express a TCR targeting MAGE-A4, a protein normally expressed only in the testis but present in certain cancers.

Unlike chimeric antigen receptor (CAR)-modified T cells, which target surface proteins on cancer cells, TCR T-cell therapies are able to target proteins normally found inside the cell by recognizing protein fragments bound to immune-related proteins on the cell surface.

The Phase I trial was designed as a dose-escalation study to assess the safety, tolerability and antitumor activity of ADP-A2M4 in patients with advanced solid tumors with expression of the MAGE-A4 protein. Patients on the trial included those with synovial sarcoma, ovarian cancer, head and neck cancer, gastric cancer, myxoid/round cell liposarcoma, non-small cell lung cancer, bladder cancer, esophageal cancer and melanoma. Participants had a median of three prior lines of systemic therapy.

The therapy achieved strong responses in particular groups of patients in the trial. Patients with synovial sarcoma saw a 43.8% OR rate and a disease control rate of more than 90%. There also was an additional patient with an unconfirmed response after the data cut-off. Median duration of response in these patients was 28 weeks and median progression-free survival was 20 weeks. Confirmed responses were also seen in patients with lung cancer and head and neck cancer.

Most patients (97.4%) experienced some treatment-related adverse events, with the most common being low blood cell counts (lymphopenia, leukopenia, neutropenia, anemia and thrombocytopenia). Half of patients experienced cytokine release syndrome. Two patients had trial-related deaths, which led to modification of the lymphodepletion regimen and eligibility criteria.

"The side effects seen on the trial were largely consistent with those typically experienced by cancer patients undergoing lymphodepleting chemotherapy and cellular therapy," said Hong. "This study is a nice proof of concept for treating solid tumors and suggests there could be a role for cellular therapies in these indications going forward."

This research is part of an ongoing strategic alliance between MD Anderson and Adaptimmune, designed to expedite the development of novel T-cell therapies for multiple cancer types. Translational research and analyses of related biomarkers continues. Results from this study led to a low-dose radiation sub-study, a Phase II trial of ADP-A2M4 in sarcoma and a Phase I trial of Adaptimmune’s next-generation T-cell therapy targeting MAGE-A4, ADP-A2M4CD8.