On October 28, 2021 Synthekine Inc., an engineered cytokine therapeutics company, reported it is advancing its IL-2 partial agonist, STK-012, into clinical investigation following clearance of its investigational new drug (IND) application by the U.S. Food and Drug Administration (FDA) (Press release, Synthekine, OCT 28, 2021, View Source [SID1234592138]).

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Synthekine will evaluate STK-012 in a Phase 1a/1b, open-label, multi-center, dose escalation study. The study will investigate STK-012 both as a monotherapy and in combination with an immune checkpoint inhibitor in individuals with advanced solid tumors.

"IL-2 is a cytokine with proven benefit as an anti-cancer therapy. However, the indiscriminate activity of IL-2 can cause severe toxicities, limiting its clinical application," said Naiyer Rizvi, M.D., chief medical officer of Synthekine. "We have designed STK-012 to uncouple the efficacy and toxicity of IL-2, and we look forward to now investigating its potential in our first clinical development program."

STK-012 is designed as an alpha/beta-biased IL-2 partial agonist to selectively stimulate antigen-activated T cells, which are associated with potent anti-tumor activity, and avoid stimulation of toxicity causing immune cells, such as natural killer cells. Synthekine has presented data at AACR (Free AACR Whitepaper) 2021 from preclinical studies demonstrating a mouse surrogate of STK-012 achieved superior tumor regression compared to both wild-type mouse IL-2 and a non-alpha-IL-2 agent, representing a different approach to biasing IL-2. In toxicity models, the mouse surrogate of STK-012, unlike these same comparators, was well tolerated and did not induce capillary leak syndrome (CLS), a dose-limiting IL-2-related toxicity which can result in death. In non-human primate models, STK-012 demonstrated a significantly improved pharmacokinetic and toxicity profile versus both aldesleukin (a recombinant IL-2 therapy) and a non-alpha-IL-2 agent.

On October 28, 2021 Foundation Medicine, Inc. reported that the company has signed agreements for in-network provider status with Humana Military and Health Net Federal Services, which administer the TRICARE health program for military members, retirees and their families (TRICARE).1,2 TRICARE is one of the largest health plans in the United States with 9.6 million beneficiaries (Press release, Foundation Medicine, OCT 28, 2021, View Source [SID1234592137]). Under the new agreements, TRICARE beneficiaries now have improved access to Foundation Medicine’s FDA-approved comprehensive genomic profiling (CGP) tests, FoundationOneCDx and FoundationOneLiquid CDx, in accordance with their approved indications for all solid tumors.

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Through tissue or blood samples, FoundationOne CDx and FoundationOne Liquid CDx evaluate more than 300 genes known to drive cancer growth and identify patients who may be eligible for specific targeted therapies, immunotherapies or clinical trials. In-network coverage of FoundationOne CDx and FoundationOne Liquid CDx testing will support broader access to precision cancer care and may lead to lower out-of-pocket costs for patients who receive any such testing in accordance with their TRICARE policy.

"We believe all patients living with advanced cancer should benefit from comprehensive genomic profiling to inform their care and these agreements are an important step forward in making that happen through improved access to testing," said Brian Alexander, MD, MPH, chief executive officer at Foundation Medicine. "We’re proud to work with Humana Military and Health Net Federal Services to ensure service members, retirees and their families have access to these critical tools in the clinic and can therefore evaluate potential treatment options for their specific cancer."

As the two regional contractors of TRICARE, Humana Military and Health Net Federal Services administer care and manage the broad regional networks of civilian and community providers. The TRICARE program brings together the health care resources of the Military Health System (MHS), including military hospitals and clinics, with a network of civilian health care providers, and provides a robust benefit for military beneficiaries, including active-duty military and their families, as well as military retirees and their families. Foundation Medicine’s agreements with Humana Military and Health Net Federal Services will help bring precision medicine treatment options to more cancer patients across the country.

About FoundationOne Liquid CDx
FoundationOne Liquid CDx is a qualitative next generation sequencing based in vitro diagnostic test for prescription use only that uses targeted high throughput hybridization-based capture technology to analyze 324 genes utilizing circulating cell-free DNA (cfDNA) isolated from plasma derived from anti-coagulated peripheral whole blood of advanced cancer patients. The test is FDA-approved to report short variants in over 300 genes and is a companion diagnostic to identify patients who may benefit from treatment with specific therapies (listed in Table 1 of the Intended Use) in accordance with the approved therapeutic product labeling. Additional genomic findings may be reported and are not prescriptive or conclusive for labeled use of any specific therapeutic product. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Patients who are negative for companion diagnostic mutations should be reflexed to tumor tissue testing and genomic alteration status confirmed using an FDA-approved tumor tissue test, if feasible. For the complete label, including companion diagnostic indications and complete risk information, please visit www.F1LCDxLabel.com.

About FoundationOne CDx
FoundationOne CDx is a next-generation sequencing based in vitro diagnostic device for detection of substitutions, insertion and deletion alterations (indels), and copy number alterations (CNAs) in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from formalin-fixed, paraffin-embedded (FFPE) tumor tissue specimens. FoundationOne CDx is for prescription use only and is intended as a companion diagnostic to identify patients who may benefit from treatment with certain targeted therapies in accordance with their approved therapeutic product labeling. Additionally, FoundationOne CDx is intended to provide tumor mutation profiling to be used by qualified health care professionals in accordance with professional guidelines in oncology for patients with solid malignant neoplasms. Use of the test does not guarantee a patient will be matched to a treatment. A negative result does not rule out the presence of an alteration. Some patients may require a biopsy. For a full list of targeted therapies for which FoundationOne CDx is indicated as a companion diagnostic, please visit View Source

On October 28, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a company applying innovative diagnostics to inform disease management decisions and improve patient outcomes, reported that the DecisionDx-Melanoma integrated test result (ITR) now includes i31-GEP for Risk of Recurrence (i31-ROR) (Press release, Castle Biosciences, OCT 28, 2021, View Source [SID1234592136]). Designed to improve the precision of treatment plans for better patient care, the i31-ROR predicts patient-specific five-year outcomes for melanoma-specific survival (MSS), distant metastasis-free survival (DMFS) and recurrence-free survival (RFS).

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DecisionDx-Melanoma is a gene expression profile (GEP) test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as risk of sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples.

Earlier this year, Castle launched the ITR for DecisionDx-Melanoma, which included i31-GEP Sentinel Lymph Node Biopsy (i31-SLNB). i31-SLNB is an independently validated algorithm that integrates clinicopathologic features with the 31-GEP score. i31-SLNB is designed to provide a more precise and personalized prediction of sentinel lymph node (SLN) positivity to guide discussions and recommendations, within current risk-based guidelines, for the SLN biopsy (SLNB) surgical procedure.

Castle has now completed independent validation of a new, separate algorithm, i31-ROR, that integrates DecisionDx-Melanoma’s 31-GEP score with the specific Breslow thickness, mitotic rate, SLN status, ulceration status and location (head and neck, extremities, trunk) of the individual patient’s tumor. The additional endpoints of RFS and DMFS, which are not currently provided by the American Joint Committee on Cancer Eighth Edition (AJCC8) staging system, are anticipated to be helpful when determining appropriate treatment pathways for each patient’s disease. The new upgraded ITR now provides both this new i31-ROR result as well as the i31-SLNB, in addition to the traditional class designation obtained with DecisionDx-Melanoma.

"Clinicians and patients look to our tests to provide clinically actionable information that better informs cancer management decisions, such as intensity of surveillance and follow-up frequency," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "And we are committed to continually reviewing this process to improve patient care, as evidenced by the introduction of our new i31-GEP for Risk of Recurrence test result.

"With this additional information, DecisionDx-Melanoma results are not only designed to provide a more precise, personalized likelihood of SLN positivity, but now also include a more individualized risk assessment, rather than an average, population-based risk estimate, that we believe can help personalize patient management decisions and overall risk assessments beyond standard melanoma staging."

About DecisionDx-Melanoma

DecisionDx-Melanoma is a gene expression profile test that uses an individual patient’s tumor biology to predict individual risk of cutaneous melanoma metastasis or recurrence, as well as sentinel lymph node positivity, independent of traditional staging factors, and has been studied in more than 5,700 patient samples. Using tissue from the primary melanoma, the test measures the expression of 31 genes. The test has been validated in four archival risk of recurrence studies of 901 patients and six prospective risk of recurrence studies including more than 1,600 patients. Impact on patient management plans for one of every two patients tested has been demonstrated in four multicenter and single-center studies including more than 560 patients. The consistent performance and accuracy demonstrated in these studies provides confidence in disease management plans that incorporate DecisionDx-Melanoma test results.

To predict risk of recurrence and likelihood of sentinel lymph node positivity, the Company utilizes its proprietary algorithms, i31-ROR and i31-SLNB, to produce an integrated DecisionDx-Melanoma test result.

Through June 30, 2021, DecisionDx-Melanoma has been ordered 78,277 times for use in patients with cutaneous melanoma. More information about the test and disease can be found at www.CastleTestInfo.com.

On October 28, 2021 Exicure, Inc. (NASDAQ: XCUR), a pioneer in gene regulatory and immunotherapeutic drugs utilizing spherical nucleic acid (SNA) technology, reported presentations at the following scientific conferences during the month of November (Press release, Exicure, OCT 28, 2021, View Source [SID1234592135]):

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TIDES EU
Title: "Development of Spherical Nucleic Acids Targeting SCN9A For the Treatment of Neuropathic Pain"
Presented by: Bart Anderson, Senior Director, R&D
Date: November 16, 2021
Time: 8:45am CET / 1:45am U.S. CST

Neuroscience 2021 (The Society for Neuroscience)
Poster 1: "Spherical Nucleic Acids Targeting FXN Induce Frataxin Expression in Models of Friedreich’s Ataxia"
Presented by: Grant Corbett, Group Lead, Neuroscience
Poster 2: "Biodistribution of Spherical Nucleic Acids in the Mouse CNS Following ICV, ICM and IT Delivery"
Presented by: Lauren Moore, Senior Scientist, Neuroscience
November 8-11, 2021

On October 28, 2021 Novocure (NASDAQ: NVCR) reported that the final patient has been enrolled in phase 3 pivotal INNOVATE-3 trial evaluating the efficacy of Tumor Treating Fields (TTFields) together with paclitaxel for treatment of patients with platinum-resistant ovarian cancer (Press release, NovoCure, OCT 28, 2021, View Source [SID1234592134]).

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"This is a major step forward for our clinical trial program and an important achievement for patients, trial investigators and our company," said William Doyle, Novocure’s Executive Chairman. "Ovarian cancer is the fifth leading cause of cancer death in women, impacting nearly 100,000 patients annually in the U.S., Europe and Japan, alone. INNOVATE-3 is the largest abdominal trial to complete enrollment in Novocure history, and we are excited to be enhancing the clinical field in support of people with this deadly disease."

Following the completion of enrollment, an independent Data Monitoring Committee (DMC) will conduct the pre-specified interim analysis pursuant to the trial protocol. Final data from the INNOVATE-3 trial is anticipated in 2023.

INNOVATE-3 is a randomized, open-label study which was designed to enroll 540 adult patients with recurrent, platinum-resist ovarian cancer. Patients have been randomized to receive either weekly paclitaxel alone or weekly paclitaxel concomitant with TTFields tuned to 200 kHz until progression. The primary endpoint is overall survival. Secondary endpoints include progression free survival, objective response rate, severity and frequency of adverse events, time to undisputable deterioration in health-related quality of life or death, and quality of life. The European Network for Gynecological Oncological Trials (ENGOT) and The GOG Foundation, Inc. collaborated with Novocure on the design and facilitation of this trial.

About Ovarian Cancer

In the U.S., ovarian cancer ranks fifth in cancer deaths among women, with approximately 24,000 women diagnosed each year. Ovarian cancer incidence increases with age, and the median age at time of diagnosis is 63 years old. Physicians use different combinations of surgery and pharmacological therapies to treat ovarian cancer, depending on the stage of the disease. Surgery is usually used in early stages of the disease and is usually combined with chemotherapy, including paclitaxel and platinum-based chemotherapy. Unfortunately, the majority of patients are diagnosed at an advanced stage when the cancer has spread outside of the ovaries to include regional tissue involvement and/or metastases. Platinum-based chemotherapy remains part of the standard of care in advanced ovarian cancer, but most patients with advanced ovarian cancer will have tumor progression or, more commonly, recurrence. Almost all patients with recurrent disease ultimately develop platinum resistance, and the prognosis for this population remains poor.

About Tumor Treating Fields

Tumor Treating Fields, or TTFields, are electric fields that disrupt cancer cell division.

When cancer develops, rapid and uncontrolled division of unhealthy cells occurs. Electrically charged proteins within the cell are critical for cell division, making the rapidly dividing cancer cells vulnerable to electrical interference. All cells are surrounded by a bilipid membrane, which separates the interior of the cell, or cytoplasm, from the space around it. This membrane prevents low frequency electric fields from entering the cell. TTFields, however, have a unique frequency range, between 100 to 500 kHz, enabling the electric fields to penetrate the cancer cell membrane. As healthy cells differ from cancer cells in their division rate, geometry and electric properties, the frequency of TTFields can be tuned to specifically affect the cancer cells while leaving healthy cells mostly unaffected.

Whether cells are healthy or cancerous, cell division, or mitosis, is the same. When mitosis starts, charged proteins within the cell, or microtubules, form the mitotic spindle. The spindle is built on electric interaction between its building blocks. During division, the mitotic spindle segregates the chromosomes, pulling them in opposite directions. As the daughter cells begin to form, electrically polarized molecules migrate towards the midline to make up the mitotic cleavage furrow. The furrow contracts and the two daughter cells separate. TTFields can interfere with these conditions. When TTFields are present in a dividing cancer cell, they cause the electrically charged proteins to align with the directional forces applied by the field, thus preventing the mitotic spindle from forming. Electrical forces also interrupt the migration of key proteins to the cell midline, disrupting the formation of the mitotic cleavage furrow. Interfering with these key processes disrupts mitosis and can lead to cell death.

TTFields are intended principally for use together with other standard-of-care cancer treatments. There is a growing body of evidence that supports TTFields’ broad applicability with certain other cancer therapies, including radiation therapy, certain chemotherapies and certain immunotherapies. In clinical research and commercial experience to date, TTFields has exhibited no systemic toxicity, with mild to moderate skin irritation being the most common side effect.

Fundamental scientific research extends across two decades and, in all preclinical research to date, TTFields has demonstrated a consistent anti-mitotic effect. The TTFields global development program includes a network of preclinical collaborators and a broad range of clinical trials across all phases, including four phase 3 pivotal trials in a variety of tumor types. To date, more than 20,000 patients have been treated with TTFields.