On December 15, 2020 Glycostem Therapeutics B.V., a leading clinical-stage company focused on the development of therapeutic off-the-shelf Natural Killer (NK) cells, reported that the first patient has been dosed in its pivotal phase I/IIa trial of oNKord for the treatment of Acute Myeloid Leukemia (AML) (Press release, Glycostem Therapeutics, DEC 15, 2020, View Source [SID1234572900]). The WiNK trial will enroll 33 AML patients at eight clinical sites based in five European countries. oNKord is the company’s first-generation off-the-shelf allogeneic NK cellular immunotherapy product. Glycostem is furthermore developing a range of second (CAR-NK) and third generation (TCR-NK) NK products in-house.

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"We are thrilled about the first patient being dosed in this pivotal trial. This important milestone potentially paves the way for a positive impact on the lives of patients with AML who are at high risk of relapse. The preliminary efficacy data obtained with oNKord is very promising and we are looking forward to the data from this study, which will allow us to draw conclusions regarding oNKord safety and tolerability and most importantly its efficacy for treatment of AML patients," tells Troels Jordansen, CEO at Glycostem.

"We are very excited about being involved in the WiNK trial and to learn what the efficacy of oNKord will be on eradicating measurable residual disease (MRD) in AML patients," tells Professor Heuser, Investigator and Head of the central laboratory for MRD assessment at the Hannover Medical School in Germany. "Currently, two thirds of MRD-positive AML patients who are in complete morphologic remission will relapse, and unfortunately, there is no cure for this group of patients if allogeneic stem cell transplantation is not an option. Therefore, the outcome of this trial is literally of vital importance and positive results could have a very significant impact on the prospects of current and future patients we are treating."

Evaluating safety, tolerability and efficacy

WiNK (ClinicalTrials.gov identifier: NCT04632316) is a prospective two-stage, open-label, single arm, multicenter phase I/IIa trial to evaluate the safety and efficacy of oNKord, an off-the-shelf, ex vivo-cultured allogeneic NK cell preparation, in 33 adults with AML who are in complete morphologic remission with residual measurable disease and with no strong indication for hematopoietic stem cell transplantation.

Stage A of the trial is designed to assess the safety and tolerability of escalating doses of oNKord in three cohorts of three subjects each. An Independent Data Monitoring Committee (IDMC) will review safety data of all treated subjects in each cohort and make recommendations before moving to the next dose. Stage B of the trial will enroll an additional 24 subjects to evaluate the safety, tolerability and efficacy of oNKord at the recommended phase II dose, as identified from stage A.

On December 15, 2020 Prelude Corporation (PreludeDxä), a leader in molecular diagnostics and precision medicine for early stage breast cancer, presented clinical outcomes data last week at the San Antonio Breast Cancer Symposium (SABCS) that further validates the DCISionRT test results of an independent study by Kaiser Permanente Northwest published earlier this year in Clinical Cancer Research (Press release, Prelude Therapeutics, DEC 15, 2020, View Source [SID1234572899]). DCISionRT is a biologic risk signature that assess the 10-yr risk of a subsequent breast cancer recurrence. A Spotlight Poster presented at SABCS, showed that the DCISionRT test reclassified 45% of patients meeting RTOG 9804 low risk or ‘good risk’ criteria for Ductal Carcinoma In Situ (DCIS) as Decision Score (DS) Elevated Risk. These patients who were reclassified by the DCISionRT test to DS Elevated Risk had clinically elevated 10-year breast cancer rates when treated without radiation therapy (RT) and demonstrated an 84% relative benefit with RT.

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The company’s Spotlight Poster, entitled DCIS biosignature reclassified patients, who met RTOG 9804 or ECOG-ACRIN E5194 low-risk clinicopathologic criteria into an elevated invasive risk group who benefited significantly from radiation therapy, was presented on Thursday, December 10 by Dr. Chirag Shah, Director of Breast Radiation Oncology and Director of Clinical Research – Radiation Oncology at Cleveland Clinic.

RTOG 9804 criteria is based on traditional clinical and pathological features and is used to identify low risk or ‘good risk’ DCIS patients. In this study, complete biomarker data was available for 535 women meeting ‘good risk’ clinicopathologic RTOG 9804-like criteria. In the DCISionRT DS Low Risk group there was no significant reduction from RT. However, in the DCISionRT DS Elevated Risk group, RT significantly reduced invasive breast cancer risk by 84%.

"In this study we examined the utility of the DCISionRT test to identify patients who otherwise met traditional ‘good-risk’ criteria but remained at an elevated invasive risk after lumpectomy," said
Dr. Shah. "The study supports the use of DCISionRT, which provides a ten-year breast event risk with and without radiation therapy after lumpectomy, as compared to traditional clinical and pathological features when making radiation therapy decisions following breast conserving surgery in patients with DCIS."

Similar results were previously reported by an independent validation of DCISionRT conducted by Kaiser Permanente Northwest (KPNW), which included a 455 patient cohort. DCISionRT reclassified approximately 50% of patients meeting ‘good risk’ criteria like RTOG 9804 as DS Elevated Risk. Women in the DS Elevated Risk category in the KPNW cohort had a 21% 10-yr invasive recurrence rate when treated with lumpectomy and without RT, and a 6% rate when receiving radiation therapy.

"We appreciate the opportunity to have worked alongside such esteemed physicians and organizations and are thrilled to announce another strong data set supporting the integration of DCISionRT into clinical practice management for DCIS," said Daniel Forche, President and CEO of PreludeDx. "Women and their physicians contemplating the next treatment steps now can make a personalized decision for radiation therapy that includes their individual tumor biology to add or omit radiation therapy after breast conserving surgery."

About DCISionRT for Breast DCIS

DCISionRT is the only risk assessment test for patients with ductal carcinoma in situ (DCIS) that predicts radiation therapy benefit. In the US, over 60,000 women are newly diagnosed with DCIS each year. DCISionRT, developed by PreludeDx and built on research that began with funding from the National Cancer Institute, enables physicians to better understand the biology of DCIS. DCISionRT combines the latest innovations in molecular biology with artificial intelligence and machine learning to assess a woman’s individual tumor biology along with other risk factors and provide a personalized recurrence risk. The test provides a Decision ScoreTM that identifies a woman’s risk as low or elevated. DCISionRT’s intelligent reporting provides a woman’s recurrence risk after breast conserving surgery alone and with the addition of radiation therapy. In turn, this new information may help patients and their physicians to make more informed treatment decisions.

On December 15, 2020 Nektar Therapeutics (NASDAQ:NKTR) reported that the first patient has been dosed in the Phase 1/2 trial of NKTR-255, Nektar’s investigational IL-15 pathway agonist, in patients with relapsed or refractory (R/R) head and neck squamous cell carcinoma (HNSCC) or colorectal cancer (CRC) at the START Center for Cancer Care in San Antonio, TX (Press release, Nektar Therapeutics, DEC 15, 2020, View Source [SID1234572897]). The study is evaluating NKTR-255 plus cetuximab in up to 80 patients at approximately 15 investigator sites in the United States and European Union.

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NKTR-255 is designed to activate the IL-15 pathway and expand Natural Killer (NK) cells as well as promote the survival and expansion of CD8+ T cells without inducing suppressive regulatory T cells. Cetuximab is a monoclonal antibody against epidermal growth factor receptor (EGFR) and is approved for the treatment of advanced HNSCC and CRC.

"An NK-cell agent such as NKTR-255 is a perfect and unique complement to monoclonal antibody therapies which induce antibody-dependent cellular cytotoxicity," said Wei Lin, MD, Head of Development at Nektar. "Our body of preclinical and clinical data for NKTR-255 demonstrates that this novel agent not only induces NK cell proliferation but also enhances their cytotoxic immune effector function. With this new Phase 1/2 study in HNSCC and CRC, we are excited to expand our NKTR-255 development program beyond the hematological setting into solid tumors."

Nektar recently presented the first clinical data for NKTR-255 at the most recent 2020 Society for Immunotherapy in Cancer (SITC) (Free SITC Whitepaper) Annual Meeting in November. The data demonstrated that NKTR-255 was well tolerated and biologically active, and treatment resulted in consistent expansion of lymphocytes, with durable and sustained increases in NK and CD8+ T cells in a highly refractory population of patients with multiple myeloma (MM) and non-Hodgkin lymphoma (NHL).

The new Phase 1b/2 study will test the combination of NKTR-255 with cetuximab in two groups of patients. One group will consist of R/R head and neck cancer patients who have progressed after treatment with platinum-based chemotherapy and a checkpoint inhibitor. The second group will include patients with metastatic colorectal cancer who have received two prior treatments for metastatic disease. The trial will begin with a dose-finding portion for the combination, which will then be expanded into dedicated cohorts for head and neck and colorectal cancer patients.

About NKTR-255

NKTR-255 is an investigational IL-15 receptor agonist designed to activate the IL-15 pathway and expand NK cells and promote the survival and expansion of memory CD8+ T cells without inducing suppressive regulatory T cells. Through optimal engagement of the IL-15Rα/IL-2Rβγ receptor complex, NKTR-255 enhances functional NK cell population and formation of long-term immunological memory, which may lead to sustained anti-tumor immune response. NKTR-255 is uniquely designed to overcome the challenges of recombinant IL-15 and other IL-15 agonists, which are rapidly cleared from the body and have shown diminishing response to successive doses.1 NKTR-255 is wholly-owned by Nektar.

On December 15, 2020 The National Comprehensive Cancer Network (NCCN) Oncology Research Program (ORP) reported four projects selected to receive funding for clinical evaluation of axitinib (Press release, NCCN, DEC 15, 2020, View Source [SID1234572895]). Axitinib, a small molecule indazole derivative, is an oral multi-targeted tyrosine kinase inhibitor of Vascular Endothelial Growth Factor (VEGF) Receptors 1, 2, and 3. NCCN issued the initial Request for Proposals and convened a Scientific Review Committee from across NCCN Member Institutions to select projects. The studies will receive funding and oversight from Pfizer.

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The following projects were selected:

Phase II Study of Axitinib + Ipilimumab in Advanced Melanoma
Zeynep Eroglu, MD, Moffitt Cancer Center
Single-arm Phase II Study of Axitinib, Avelumab, and Bavituximab in Advanced HCC
David Hsieh, MD, UT Southwestern Simmons Comprehensive Cancer Center
Phase II Study of Axitinib + PD-1 Blockade in Mucosal Melanoma with Adaptive Phase I Escalation in Select Progressors
Alexander Shoushtari, MD, Memorial Sloan Kettering Cancer Center
Phase I-II Study of Hepatic Chemoembolization With Irinotecan-Loaded Drug-Eluting Microspheres (DEBIRI) Plus Axitinib and Hydrochlorquine for Liver-Dominant Metastatic Adenocarcinoma Of The Colon And Rectum
Michael Soulen, MD, Abramson Cancer Center at the University of Pennsylvania
"We’re particularly interested in learning more about the efficacy of axitinib in combination with various other anti-cancer agents, that may exploit its specific pharmacokinetics," said Wui-Jin Koh, MD, Chief Medical Officer, NCCN. "These innovative studies will add to our knowledge base for treating challenging cancer presentations, as part of our ongoing exploration into how to improve patient outcomes. All of the selected researchers should be commended for their meritorious proposals."

The projects are set to begin by August 2021.

The NCCN ORP fosters innovation and knowledge discovery that improves the lives of people with cancer and supports preclinical, translational, clinical research and quality improvement projects in oncology at NCCN Member Institutions. In an effort to improve collaboration in cancer research, the NCCN ORP also maintains a shared resources website and an informed consent database. For more information, visit NCCN.org/orp.

On December 15, 2020 Qualigen Therapeutics, Inc. (Nasdaq: QLGN), a biotechnology company focused on developing novel therapeutics for the treatment of cancer and infectious diseases, reported that the United States Patent and Trademark Office has issued a patent entitled "Anti-Nucleolin Agent-Conjugated Nanoparticles as Radio-Sensitizers and/or MRI Contrast Agents" regarding the Company’s ALAN (Aptamer-Linked Anti-Nucleolin) technology (Press release, Qualigen, DEC 15, 2020, View Source [SID1234572894]). This patent issued to the University of Louisville (UofL) protects the ALAN technology for use with cancer radiation therapy and for imaging tumors utilizing magnetic resonance imaging (MRI). The novel ALAN technology has several other potential applications, including its use as a monotherapy for the treatment of cancer and as a vehicle to deliver other anticancer compounds directly to tumors. In 2018, Qualigen obtained exclusive worldwide rights from the UofL for the use of the ALAN technology.

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The gold nanoparticle component of ALAN is believed to enhance radiation therapy by "magnifying" the effects of radiation on the targeted tumor cells with the potential to justify lower radiation exposure and, in turn, decrease side effects. ALAN may also potentially be used in combination with MRIs to provide higher-resolution images of solid tumors and tumor cells as special imaging dyes attach to the gold nanoparticle compound.

"With the issuance of this patent, we continue to build our intellectual property portfolio as a key component to protect our technologies under development," stated Michael Poirier, Qualigen’s Chairman, Chief Executive Officer and President. "ALAN is a valuable therapeutic platform technology that may be applied in numerous indications. Currently, we are evaluating strategic options on how to develop and monetize these additional applications while we continue to advance ALAN in our development pipeline against acute myeloid leukemia."

ALAN is a DNA aptamer-based anticancer drug candidate that combines the DNA aptamer AS1411 with a gold nanoparticle to dramatically increase its potency. This drug candidate has the potential to target and destroy tumor cells in a wide variety of cancer types with minimal side effects. The Company plans to commence Phase 1 human trials with ALAN in 2021 in patients with acute myeloid leukemia, its lead indication.

"The issuance of this patent for ALAN further protects this technology’s potential broad applicability as a treatment for cancer," added Paula Bates, PhD, Professor of Medicine at UofL. "We look forward to our continued collaboration with Qualigen as we plan to enter this drug candidate into clinical trials as a therapeutic next year. We believe ALAN has the potential to be more targeted than available cancer treatments with the ability not to harm normal healthy cells resulting in less side effects for the patient."

Qualigen currently has 58 issued and pending patents and has in-licensed rights to a further 42 issued and pending patents.