On December 11, 2020 Exact Sciences Corp. (NASDAQ: EXAS) reported the presentation of new data at the virtual 2020 San Antonio Breast Cancer Symposium (SABCS) building on the clinical value of the Oncotype DX Breast Recurrence Score test (Press release, Exact Sciences, DEC 11, 2020, View Source [SID1234572659]). These data highlight the role of the test in further individualizing treatment decisions in early breast cancer.

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"These latest presentations, including data from the RxPONDER trial, further highlight the unique value of the Recurrence Score result in providing critical information to personalize and improve the quality of treatment decisions in node-negative and node-positive early breast cancer," said Rick Baehner, MD, chief medical officer of Precision Oncology at Exact Sciences.

Five-year outcomes from ADAPT study show that not all clinically high-risk patients with node-negative or node-positive disease need chemotherapy

First efficacy results from the ADAPT study (4,691 patients) were presented at SABCS.[i]Patients were all considered candidates for chemotherapy by traditional parameters and were stratified using the Oncotype DX test and changes in the immunohistochemical prognostic marker Ki67 after three weeks of pre-operative anti-hormonal therapy. Patients with clinically high risk node-negative disease, and node-positive disease with up to 3 positive nodes, were treated with anti-hormonal therapy alone if the Recurrence Score result was 0–11 or if the Recurrence Score result was 12-25 with a Ki67 response. This group of patients had, regardless of their age, favorable outcomes with anti-hormonal therapy alone, with 5-year distant disease-free survival of 96%.

Another analysis from the ADAPT trial also presented at SABCS evaluated 864 breast cancer patients who received neoadjuvant chemotherapy primarily based on their Recurrence Score result.[ii] These results from a large neoadjuvant trial showed that the Recurrence Score result is a strong predictor of response to chemotherapy as assessed by the rate of pathologic complete response (no residual invasive tumor).

ADAPT is one of the largest prospective, randomized studies in early-stage breast cancer and was conducted by the West German Study Group (WSG) in 80 centers across Germany. It utilized a pioneering trial design to assess individualization of (neo)adjuvant decision-making.

"Our study shows the unique value of the complementary biological information provided by the Oncotype DX test and sequential Ki67 testing. Risk stratification using the Recurrence Score result and changes in Ki67 after brief pre-operative anti-hormonal therapy allows us to identify those patients with node-negative or node-positive disease who can be spared the toxicity and side effects of chemotherapy without a negative impact on treatment outcome," said Prof. Nadia Harbeck, Scientific Director of the WSG and Head of the Breast Centre at LMU Klinikum Munich (LMU), Germany. "This is especially important for patients who would be considered at high risk of relapse based on traditional clinical parameters."

New patient-specific meta-analysis provides individualized estimates for both prognosis and absolute chemotherapy benefit in node-negative breast cancer

A new patient-specific meta-analysis of data from more than 10,000 patients with node-negative disease assessed individualized estimates of distant recurrence risk and absolute chemotherapy benefit based on the integration of the Recurrence Score result with clinicopathologic features.[iii]This analysis builds on the practice-changing results from the TAILORx study, which prospectively defined the groups of patients who will and will not benefit from chemotherapy.

The meta-analysis was conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) and was presented in an oral session at SABCS by lead author Joseph A. Sparano, M.D., associate director for clinical research at Albert Einstein Cancer Center and associate chair for clinical research in the department of oncology at Montefiore Health System in New York, and leader of the TAILORx study for the ECOG-ACRIN Cancer Research Group. The data was published concurrently in the December 2020 issue of the Journal of Clinical Oncology.

The patient-specific meta-analysis estimates will initially be made available to physicians in the United States, starting in December 2020, as an online educational tool called RSClin. The tool provides a more individualized prediction of absolute chemotherapy benefit that can enhance treatment decisions, particularly for patients whose Recurrence Score result is close to the TAILORx defined cut-off point of 25. By presenting the data in a new, easy-to-understand, visual format, RSClin empowers physicians with information that may be used to facilitate treatment conversations and decision-making with patients.

"As confirmed in TAILORx, for the great majority of patients, treatment based on the Recurrence Score result alone is clear," said Dr. Sparano. "The RSClin tool, which now incorporates data from TAILORx to reflect contemporary treatment outcomes, provides individualized estimates for both risk of distant recurrence and absolute chemotherapy benefit and continues to demonstrate the role of TAILORx in informing early-stage breast cancer treatment."

ECOG-ACRIN conducted the analysis primarily with funding from the National Cancer Institute. Mention of commercial products does not imply endorsement by the U.S. government. Additional support was provided by the Breast Cancer Research Foundation, the Komen Foundation, and the Breast Cancer Research Stamp issued by the United States Postal Service.

On December 11, 2020 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported the opening for patient screening and enrollment of the IMpactMF Phase 3 clinical trial of imetelstat, a first-in-class telomerase inhibitor, in refractory myelofibrosis (MF) (Press release, Geron, DEC 11, 2020, View Source [SID1234572658]).

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"As Geron’s second registration-enabling Phase 3 trial in hematologic myeloid malignancies, the IMpactMF trial represents a milestone for our Company," said Aleksandra Rizo, M.D., Ph.D., Geron’s Chief Medical Officer. "The IMpactMF trial will evaluate imetelstat in a poor-prognosis refractory MF patient population to confirm the clinical benefits of extended overall survival and symptom improvement observed in our IMbark Phase 2 trial, as well as the reductions in abnormal clones and mutation burden demonstrating disease-modifying activity of imetelstat."

Geron plans for IMpactMF to evaluate imetelstat compared to best available therapy (BAT) in approximately 320 patients with Intermediate-2 or High-risk MF. Patients eligible for the trial will be required to be non-responsive, or refractory, to treatment with a JAK inhibitor. The primary efficacy endpoint for the Phase 3 trial is overall survival (OS). Secondary endpoints include symptom response, spleen response, progression free survival, duration of response, safety, pharmacokinetics and patient reported outcomes. Geron plans to engage over 150 sites to participate in IMpactMF across North America, South America, Europe and Asia, with the majority of clinical sites expected to be open for screening and enrollment in 2021, subject to potential delays or interruptions associated with the evolving and uncertain effects of the COVID-19 pandemic.

To learn more about IMpactMF and whether the study is enrolling patients in your area, please visit www.clinicaltrials.gov.

About Myelofibrosis (MF)

Myelofibrosis, a type of myeloproliferative neoplasm, is a chronic blood cancer in which abnormal or malignant precursor cells in the bone marrow proliferate rapidly, causing scar tissue, or fibrosis, to form. People with MF may have abnormally low or high numbers of circulating red blood cells, white blood cells or platelets, and abnormally high numbers of immature cells in the blood or bone marrow. MF patients can also suffer from debilitating constitutional symptoms, such as drenching night sweats, fatigue, severe itching, or pruritus, abdominal pain, fever and bone pain.

Approximately 70% of MF patients are classified as having Intermediate-2 or High-risk disease, as defined by the Dynamic International Prognostic Scoring System Plus. There are more than 35,000 patients worldwide and more than 13,000 patients in the U.S. living with Intermediate-2 or High-risk MF. The only drug therapies approved for treating these MF patients are JAK inhibitors. Currently, MF patients who fail or no longer respond to JAK inhibitor treatment have no or limited options, resulting in shortened median overall survival.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic myeloid malignancies. Phase 2 clinical data strongly suggest that imetelstat has disease-modifying activity through the apoptosis of malignant stem and progenitor cells, which allows potential recovery of normal hematopoiesis. Geron is currently conducting two registration-enabling Phase 3 clinical trials of imetelstat: IMerge, a Phase 2/3 trial in lower risk myelodysplastic syndromes (MDS), and IMpactMF, a Phase 3 trial in refractory myelofibrosis (MF). Imetelstat has been granted Fast Track designation by the United States Food and Drug Administration for both the treatment of patients with non-del(5q) lower risk MDS who are refractory or resistant to an erythropoiesis-stimulating agent and for patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus kinase (JAK) inhibitor treatment.

On December 11, 2020 SELLAS Life Sciences Group, Inc. (Nasdaq: SLS) ("SELLAS" or the "Company"), a clinical-stage biopharmaceutical company focused on the development of novel cancer immunotherapies for a broad range of cancer indications, reported final data with up to 6 months follow-up from a Phase 2 randomized trial (the VADIS study) of the Company’s nelipepimut-S (NPS) in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) in women with ductal carcinoma in situ (DCIS) of the breast who are HLA-A2+ or A3+ positive, express HER2 at IHC 1+, 2+, or 3+ levels, and are pre- or post-menopausal (Press release, Sellas Life Sciences, DEC 11, 2020, View Source [SID1234572655]). This investigator-sponsored trial randomized patients to receive, prior to surgery, either GM-CSF followed by NPS two weeks later or GM-CSF alone.

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Preliminary data previously reported showed that treatment with even a single dose of NPS was capable of newly inducing NPS-specific cytotoxic T-lymphocytes (CTLs) in peripheral blood in DCIS patients. The updated data, based on a 6-month follow-up, demonstrate that CD8+ T-cell responses persist long-term post-NPS treatment, with treated patients retaining and modestly enhancing their antigen-specific immune response. When compared to baseline (BL, prior to investigational agent administration), the relative frequency of NPS-specific CD8 CTLs as a percentage (NPS-CLT%) in peripheral blood at the 1-month and 6-month post-operative time-points increased in the NPS+GM-CSF group (n=9) by 11- and 14-fold: 0.01+0.02% [BL] vs. 0.11+0.12% [1-mo] and 0.14+0.12% [6-mo], respectively, while in the GM-CSF alone group (n=4) the NPS-CLT% in peripheral blood increased by only 2.25- and 3.75-fold: 0.04+0.07% [BL] vs. 0.09+0.15% [1-mo] and 0.15+0.03% [6-mo], respectively.

For the NPS+GM-CSF group, the differences in absolute NPS-CTL% mean values between baseline and 1- or 6-months post-vaccination were statistically significant, with p-values of 0.039 and 0.0125, respectively. The relative change in NPS-CTL% mean values at 6 months post-vaccination was +1,300+450% for the NPS+GM-CSF group vs. 250+150% in the GM-CSF alone group, which was highly statistically significant in favor of the NPS+GM-CSF group: p=0.000094.

"These data confirm that NPS confers long-term immune response in DCIS patients, with continued, and in fact slightly augmented, antigen-specific T-cell response for up to 6 months post-vaccination in a randomized setting," said Angelos M. Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "One of the main limitations of cancer vaccines has traditionally been the short duration of the immune response, especially for CD8+ T-cells. With these new data, we believe that a single course of NPS treatment can result in robust and lasting immunity to HER2-expressing breast cancer. In the VADIS study, immune responses emerged and were sustained even in DCIS patients with low levels of HER (IHC 1+ or 2+) expression. These data further support our belief that NPS, by preferentially inducing adaptive immunity and through its potential synergy with trastuzumab, enhances cell killing."

The VADIS study enrolled 13 patients, with nine patients receiving NPS plus GM-CSF and four patients receiving GM-CSF only. The NPS-CLT% was measured in the peripheral blood by a sensitive and specific assay using dextramer staining followed by flow cytometry, both at baseline (before vaccination or GM-CSF), as well as at 30 (+7) and 180 (+7) days after surgery. Further data from additional analyses of select histologic and molecular biomarkers will be presented in a future scientific meeting.

There were no drug-related unexpected serious adverse reactions in the study. The overall adverse event profile of the NPS+GM-CSF combination was similar to the adverse event profile seen with GM-CSF alone. Almost all patients in both arms experienced at least Grade 1 toxicities, and the incidence of Grade 2 toxicities was 6.7% in the GPS+GM-CSF arm and 10.7% in the GM-CSF only arm.

"These results further support the case for continued development of NPS in HER2-expressing breast cancer, as well as potentially other HER2-bearing cancers," said Elizabeth A. Mittendorf, MD, PhD, Rob and Karen Hale Distinguished Chair in Surgical Oncology, Director of Research, Breast Surgical Oncology Brigham and Women’s Hospital, Director, Breast Immuno-Oncology Program Dana-Farber/Brigham and Women’s Cancer Center, and the Principal Investigator of the VADIS trial. "In patients with DCIS, a single inoculation with NPS+GM-CSF can induce in vivo immunity and a continued antigen-specific T-cell response. These data provide support for further testing of NPS+GM-CSF in the neoadjuvant and adjuvant settings in an attempt to prevent invasive recurrence in DCIS," added Dr. Mittendorf.

About the VADIS spotlight poster presentation (PD11-09)

The VADIS data will be presented today, December 11, at the Virtual 2020 Annual San Antonio Breast Cancer Symposium (SABCS)
Title: Vadis trial: phase II trial of Nelipepimut-S peptide vaccine in women with DCIS of the breast.
Authors: O’Shea AE, Clifton GT, Qiao N, Heckman-Stoddard B, Wojtowicz M, Dimond E, Bedrosian I, Weber D, Husband A, Pastorello R, Vornik L, Peoples G, Mittendorf EA.
Presenter: Anne E. O’Shea, MD
Poster Discussion No.: PD11-09
Session Date – Time: Friday, December 11, 2020: 2:15 pm – 3:30 pm CST
Website: www.sabcs.org

About the Phase 2 VADIS Trial

This Phase 2 randomized trial is sponsored and operationalized by the National Cancer Institute (NCI) to study NPS’ potential clinical effects in earlier-stage disease. Patients are randomized to receive, prior to surgery, either GM-CSF followed by NPS two weeks later or GM-CSF alone. The primary endpoint of the trial is the difference in the frequency of newly induced NPS-cytotoxic T lymphocytes (CTL; CD8+ T-cell) in peripheral blood between the two arms of the study, using a dextramer assay. Secondary endpoints to be compared between the two arms include the nature and incidence of adverse events and in vivo immune response to NPS, in addition to other select histologic and molecular biomarkers.

About DCIS

DCIS is defined by the NCI as a noninvasive condition in which abnormal cells are found in the lining of a breast duct and have not spread outside the duct to other tissues in the breast. DCIS is the most common type of breast neoplasm with malignant potential. In some cases, DCIS may become invasive cancer and spread to other tissues and, currently, it is not possible to know which lesions could become invasive. Current treatment options for DCIS include breast-conserving surgery and radiation therapy with or without tamoxifen, breast-conserving surgery without radiation therapy, or total mastectomy with or without tamoxifen. Tamoxifen is given in cases with hormone receptor positivity only. No targeted or immune therapies have shown any definitive clinical activity in DCIS to date. The current standard treatment aims at forestalling the progression of DCIS to invasive cancer. In approximately 15-25% of cases progression does occur. DCIS is diagnosed in more than 60,000 women each year in the United States, comprising 1 in 5 newly diagnosed cases of breast cancer.

On December 11, 2020 In a spotlight poster discussion at the 2020 San Antonio Breast Cancer Symposium (SABCS), Myriad Genetics (NASDAQ: MYGN), a global leader in molecular diagnostics and precision medicine, reported a new study that shows how its myRisk Hereditary Cancer and riskScore tests can better inform individualized clinical screening and prevention strategies for women at risk of developing breast cancer (Press release, Myriad Genetics, DEC 11, 2020, View Source [SID1234572653]). The new Myriad study highlights how riskScore, a proprietary tool used to evaluate a woman’s risk of developing breast cancer, can accurately provide breast cancer risk information into a personalized assessment model for women carrying a pathogenic variant (PV) in the ATM gene.

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"This new study will enable a highly personalized risk calculation for patients who carry mutations in the ATM gene," said Nicole Lambert, president of Myriad Genetic Laboratories. "As a result, women carrying gene mutations will be able to make more informed choices about how to manage their risk; if increased surveillance is sufficient or if they would consider surgical options."

Myriad’s riskScore test combines data from 20 years of genome-wide association studies with a validated algorithm that uses personal and family history. riskScore is performed in conjunction with Myriad’s myRisk Hereditary Cancer test, where myRisk identifies people who carry specific cancer-linked genetic mutations.

A summary of the study is below. Follow Myriad on Twitter via @myriadgenetics and keep up to date with SABCS meeting news and updates by using the #SACBS20 hashtag.

riskScore Poster at SABCS
Title: Development of a breast cancer risk assessment model for ATM mutation carriers incorporating Tyrer-Cuzick and a polygenic risk score
Program Number: PD10-09
Session Title: Spotlight Poster Discussion 10
This study highlights the development of a comprehensive breast cancer risk model for ATM PV carriers incorporating an 86-variant PRS, along with family history and clinical information captured by Tyrer-Cuzick (a tool used to calculate the risk of breast cancer). The study found that with ATM PV carriers (N=216), a comprehensive model allowed for differentiation of carriers into low, moderate, and high breast cancer risk categories (See figure 1 below).

To view Figure 1. Remaining Lifetime Risk for ATM PV Carriers, please visit the following link: View Source

About riskScore
riskScore is a 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 prospectively validated in our laboratory to predict breast cancer risk in women of European descent. This data is then combined with a personal history and family history algorithm, the Tyrer-Cuzick model, to provide an individualized breast cancer risk assessment. Myriad is committed to advancing the validation of risk-assessment tools and making them available to all women, regardless of ancestry.

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 December 11, 2020 BioCryst Pharmaceuticals, Inc. (Nasdaq: BCRX) reported that the company will present at the JMP Securities Hematology Summit, which is being conducted as a virtual event, on Tuesday, December 15, 2020 at 3:30 p.m. ET (Press release, BioCryst Pharmaceuticals, DEC 11, 2020, View Source [SID1234572652]).

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Links to a live audio webcast and replay of the presentation may be accessed in the Investors section of BioCryst’s website at http://www.biocryst.com.