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Polatuzumab Vedotin Achieved Primary Endpoint in the Japanese Phase II study for Relapsed or Refractory Diffuse Large B-cell Lymphoma

On February 13, 2020 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that polatuzumab vedotin in combination with bendamustine and rituximab (hereafter, BR therapy) achieved the primary endpoint of complete response rate (CRR) by PET-CT at the timing of Primary Response Assessment (PRA) in the Japanese Phase II study (JO40762/P-DRIVE study) (Press release, Chugai, FEB 13, 2020, View Source [SID1234554250]). P-DRIVE is an open label, single-arm study to evaluate the combination therapy of polatuzumab vedotin with BR therapy as a treatment for people with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Combination of polatuzumab vedotin and BR therapy observed no new safety signals in the study compared with the previous studies for polatuzumab vedotin.

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"We are very pleased that polatuzumab vedotin in combination with BR therapy showed efficacy in treating relapsed or refractory DLBCL patients," said Chugai’s Executive Vice President, Co-Head of Project & Lifecycle Management Unit, Dr. Yasushi Ito. "About 40% of patients experience relapse of the disease after standard therapy and subsequent treatment options are limited. Chugai is committed to file for approval based on these results to provide patients with this potential treatment option as early as possible."

The Ministry of Health, Labour and Welfare granted the Orphan Drug designation for polatuzumab vedotin in DLBCL in November, 2019. Polatuzumab vedotin was granted accelerated approval in the US in June, 2019 and conditional marketing authorization in EU in January, 2020 respectively. In addition to the P-DRIVE study, the global phase III POLARIX study in patients with untreated DLBCL is ongoing in Japan.

Chugai Receives Orphan Drug Designation for Polatuzumab vedotin in Diffuse Large B-Cell Lymphoma from the MHLW (Press release issued by Chugai on November 20, 2019)
View Source

About JO40762 (P-DRIVE) study
JO40762 (P-DRIVE) is an open label, single-arm study investigating polatuzumab vedotin in combination with BR therapy in 35 patients with relapsed or refractory DLBCL. Primary endpoint is investigator’s assessment of CRR by PET-CT at the timing of PRA (six to eight weeks after last administration of the investigational drugs). Patients received treatment for one cycle of three weeks and was administered up to a total of 6 cycles.

About polatuzumab vedotin
Polatuzumab vedotin is a first-in-class anti-CD79b antibody-drug conjugate (ADC), comprising the anti-CD79b humanized monoclonal antibody and a tubulin polymerization inhibitor attached together using a linker. The CD79b protein is expressed specifically in the majority of B-cells, making it a promising target for the development of new therapies1, 2). Polatuzumab vedotin binds to CD79b and destroys these B-cells through the delivery of an anti-cancer agent, which is thought to suppress the effects on normal cells3, 4). Polatuzumab vedotin is being developed by Roche using Seattle Genetics’ ADC technology and is currently being investigated for the treatment of several types of non-Hodgkin’s lymphoma.

About diffuse large B-cell lymphoma (DLBCL)
DLBCL is one of the histologic subtypes of non-Hodgkin’s lymphoma (NHL), which is categorized as aggressive disease that progresses on a monthly basis. DLBCL is the most common form of NHL, accounting for 30-40 percent of NHL5-7). DLBCL frequently occurs in middle-aged and older people, mainly in their 60’s8). The median age at diagnosis has been reported to be 649).

The combination of rituximab and chemotherapy is the standard therapy for untreated DLBCL; however, recurrence has been observed in about 40% of the patients due to insufficient therapeutic effect10). In addition, although autologous stem cell transplantation (ASCT) is recommended in eligible patients with recurrent or refractory DLBCL, ASCT cannot be performed in about half of these patients due to failure of salvage chemotherapy prior to ASCT11). Furthermore, no standard therapy has been established for patients ineligible for ASCT due to reasons including age or complications12).

Salvage chemotherapy: A therapy mainly used in patients with hematologic malignancy who experienced no therapeutic effects (refractory), or recurrence/relapse of the disease is referred to as a salvage chemotherapy or salvage therapy. Applicable treatment may vary depending on the type of cancer, most of which will be combination therapies consisting of multiple drugs including anticancer agents13).

About orphan drugs
Based on Pharmaceuticals and Medical Devices Law, orphan drugs are designated by the Minister of Health, Labour and Welfare and granted priority review. The designation criteria are as follows: The number of patients who may use the drug is less than 50,000 in Japan; The drug is indicated for the treatment of serious diseases and there is a significant medical value such as no alternative appropriate drug or treatment, or high efficacy or safety expected compared to existing products; there is a theoretical rationale for using the product for the targeted disease and the development plan is reasonable.

Editas Medicine and Sandhill Therapeutics, Inc. Announce Collaboration to Develop Engineered Cell Medicines to Treat Cancer

On January 13, 2019 Editas Medicine, Inc. (Nasdaq: EDIT), a leading genome editing company, and Sandhill Therapeutics, Inc., a cellular immuno-oncology company, reported a strategic research collaboration, license, and option agreement to combine their respective genome editing and cell therapy technologies to discover, develop, and manufacture allogeneic engineered natural killer (NK) cells and non-alpha beta T cell medicines for the treatment of cancer (Press release, Editas Medicine, FEB 13, 2020, View Source [SID1234553822]).

This collaboration brings together Editas Medicine’s leading genome editing technology and Sandhill’s BINATE product process, a novel universal donor technology to extract, isolate, and expand NK cells and non-alpha beta T cells, to develop novel medicines for the treatment of solid tumor cancers.

"We are excited to work with Sandhill, combining CRISPR-based genome editing with BINATE cells to accelerate the development of numerous, transformative medicines for people with cancer and improve patient outcomes," said Charles Albright, Ph.D., Executive Vice President and Chief Scientific Officer, Editas Medicine. "We continue to increase our commitment to oncology, and we believe our portfolio of multiple immune system cell types, including T cells, NK cells, and induced pluripotent stem cells (iPSCs), will be effective in making the next generation of allogeneic medicines to fight many common cancers."

"The team at Editas Medicine has one of the most innovative technology platforms, and we look forward to combining our technologies to create new medicines for the treatment of cancer. Together, we are dedicated to transforming cellular immuno-oncology and developing new therapies," said Annemarie Moseley, M.D., Ph.D., Chief Executive Officer, Sandhill Therapeutics, Inc.

Under the terms of the agreement, Editas Medicine obtains an exclusive license to Sandhill’s technology to research, develop and commercialize immuno-oncology engineered cell medicines for solid tumors originating within a given area of the body and an option to expand such license to two additional areas. In return, Sandhill will receive an upfront payment, development and sales-based milestone payments, and royalties on sales of resulting Editas products.

RBC Capital Markets acted as exclusive financial advisor to Sandhill for the transaction.

Additional product patent in the US for HyNap-Dasa

On February 12, 2020 Xspray Pharma (Nasdaq First North Growth Market: XSPRAY) reported that the United States Patent and Trademark Office (USPTO) has granted Xspray a new US patent for HyNap-Dasa (Press release, Xspray, FEB 12, 2020, View Source [SID1234649566]). The new patent, US 10,555,937, covers the pharmaceutical composition of the company’s primary product candidate, HyNap-Dasa. This is Xspray’s fourth product patent in the United States, which is the company’s main market. The patent is valid until January 11, 2033.
"This new patent on our most important market is yet another confirmation of our innovative development work. The formal clinical bioequivalence of the company’s primary product candidate HyNap-Dasa, which has been previously communicated, means that the patent further strengthens our position in negotiations with potential partners", says Per Andersson, CEO of Xspray.

Xspray strives to obtain patents for both composition and technology and this new patent claims an amorphous solid dispersion (pharmaceutical composition) of dasatinib.

"Our strategic patent work will generate additional patents in the United States on our product candidates in the near future. The new HyNap-Dasa patent makes it significantly more difficult for other companies to launch a dasatinib product based on amorphous solid dispersion in the United States during the lifetime of the patent, i.e. up until January 2033", Per Andersson concludes.

Cue Biopharma to Present at the Biomarkers Series UK

On February 12, 2020 Cue Biopharma, Inc. (NASDAQ: CUE), a clinical-stage biopharmaceutical company engineering a novel class of injectable biologics to selectively engage and modulate targeted T cells within the body, reported Dr. Mary Simcox, vice president of translational biology and early development, will give a presentation highlighting the strategy and tactical details for testing CUE-101, the company’s lead biologic drug candidate, in a first-in-human Phase 1 trial (NCT03978689) at the Biomarkers Series UK taking place on Feb. 18-20, 2020 at the Manchester Central Convention Complex (Press release, Cue Biopharma, FEB 12, 2020, View Source [SID1234608305]). CUE-101 is designed to directly engage and activate T cells in the body to target HPV16-driven recurrent/metastatic head and neck squamous cell carcinoma (HNSCC), enabled by the company’s proprietary therapeutic platform Immuno-STAT (Selective Targeting and Alteration of T cells).

Presentation Details
Title: CUE-101 Phase 1 Trial in HNSCC Patients: Novel Immunotherapy Enabled by Patient Stratification & Pharmacodynamic Biomarkers
Session: Biomarker Congress Workshop, End-user Session, Designing/Applying a Biomarker Plan in Drug Development
Presenter: Mary Simcox, Ph.D., vice president of translational biology and early development
Date & Time: Feb. 18 at 4:15 p.m. GMT

"This presentation focuses on the importance of conducting early clinical immuno-oncology trials that are informed by detailed biomarker analyses, which characterize the mechanism of action and provide guidance on how the drug is used to maximize the potential for clinical benefit in cancer patients," said Ken Pienta, M.D., acting chief medical officer of Cue Biopharma. "The CUE-101 Phase 1 protocol includes implementation of multiple technologies and multiple industry and academic partners in the investigation of pharmacodynamic, response prediction, patient selection and response monitoring biomarkers. These critical biomarker data will be collected with the aim to discover correlative pharmacodynamic and response prediction markers to optimize the probability of clinical success and development of a promising and potentially new and transformative therapeutic."

About the CUE-100 Series
The CUE-100 series consists of Fc-fusion biologics that incorporate peptide-MHC (pMHC) molecules along with rationally engineered IL-2 molecules. This singular biologic is designed to selectively target, activate and expand a robust repertoire of tumor-specific T cells directly in the patient. The binding affinity of IL-2 for its receptor has been deliberately attenuated to achieve preferential selective activation of tumor-specific effector T cells while reducing potential for effects on regulatory T cells (Tregs) or broad systemic activation, potentially mitigating the dose-limiting toxicities associated with current IL-2-based therapies.

About Immuno-STAT
Immuno-STAT biologics are designed for targeted modulation of disease-associated T cells in the areas of immuno-oncology and autoimmune disease. Each of our biologic drugs is designed using our proprietary scaffold comprising: 1) a peptide-MHC complex (pMHC) to provide selectivity through interaction with the T cell receptor (TCR), and 2) a unique co-stimulatory signaling molecule to modulate the activity of the target T cells.

The simultaneous engagement of co-stimulatory molecules and pMHC binding mimics the signals delivered by antigen presenting cells (APCs) to T cells during a natural immune response. This design enables Immuno-STAT biologics to engage with the T cell population of interest, resulting in highly targeted T cell modulation. Because our drugs are delivered directly in the patient’s body (in vivo), they are fundamentally different from other T cell therapeutic approaches that require the patients’ T cells to be extracted, stimulated and expanded outside the body (ex vivo), and reinfused in an activated state.

NETRF funds $3.5 million in research to advance neuroendocrine tumor treatment

On February 12, 2020 The Neuroendocrine Tumor Research Foundation (NETRF), Boston, MA, reported $3.5 million in neuroendocrine tumor (NET) research grants to fund 12 projects around the world in pursuit of more precise treatments for this uncommon cancer affecting an estimated 171,000 Americans (Press release, NETRF, FEB 12, 2020, View Source [SID1234554385]).

After investing $26 million in research during the past 15 years, NETRF has helped to establish the NET knowledge base needed to expand the exploration of improved treatments, according to Elyse Gellerman, NETRF chief executive officer. "We can see real momentum in this new round of grants. We hope the discoveries from these projects will lead to improved treatment options for patients."

NETRF is supporting a new pioneering approach to NET immunotherapy with a Petersen Accelerator Award to Steven Libutti, MD, Rutgers Cancer Institute of New Jersey, to characterize a novel immune regulator called B7x to determine whether it has a role in shutting off the body’s immune response to fight against pancreatic NETs.

This round of funding features multiple new fronts for NETRF. To help grow the NET scientific workforce, the Foundation granted two inaugural Mentored Awards for early career researchers, one of which was funded by an educational grant from Ipsen. There were also new areas of NET inquiry. For the first time, NETRF is funding pheochromocytoma and paraganglioma research, including an evaluation of a novel radiotracer for imaging adrenal NETs.

NETRF also funded four research projects in lung NETs, an area that has not previously received the attention of other NET sites. These lung studies include:

Conducting single-cell genomic analyses to understand how lung NETs form, grow, and spread.
Mapping the cellular networks of typical and atypical lung NETs to find biomarkers that help predict a tumor’s aggressiveness.
Characterizing the molecular makeup of a newly identified, aggressive lung NET called "supra-carcinoid."
Determining the sociodemographic and geographic patterns of lung NETs in California.
"Advances in NET research have been hampered by the lack of effective laboratory disease models, and a limited understanding of the molecular and genetic profiles of NETs," said John Kanki, PhD, NETRF director of research. "Now that we are making strong headway along these lines, we can finally begin to drill deeper with greater specificity, to identify and explore new strategies for treating NETs."

NET tumors require the expansion of new blood vessels in order to grow and spread and two new grants explore new therapies that target developing tumor blood vessels. Researchers at Vanderbilt University will explore the potential efficacy of a combination therapy testing a drug known to affect the formation of new blood vessels (cabozantinib) together with an experimental drug called CB-839. At Columbia University Medical School, scientists will conduct preclinical laboratory experiments to test whether turning off two complementary blood vessel-forming processes together can improve therapeutic efficacy in pancreatic NETs.

NETRF also approved grants to study a potential cause of small intestinal multifocal tumors and to evaluate the role of the gut microbiome in carcinoid syndrome.

Seventy-five percent of the grants were awarded to research institutions that are new to NETRF including five grants funding international research at Erasmus MC, University Medical Center Rotterdam, Netherlands; Hebrew University of Jerusalem, Israel; International Agency for Research on Cancer (IARC-WHO), Lyon, France; Istituto Auxologico Italiano – Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy; and Weizmann Institute of Science, Rehovot, Israel.

Seven of the 12 grants fund innovative NET research at American academic institutions, including Columbia University Medical Center, New York, NY; Dana-Farber Cancer Institute, Boston, MA; Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; University of California, San Francisco, CA; Tufts Medical Center, Boston, MA; University of Michigan, Ann Arbor, MI; and Vanderbilt University Medical Center, Nashville, TN.

The NETRF grant process is a competitive and structured peer-reviewed process. The Foundation is currently accepting applications for its next grant cycle. Applications must be received by March 9, 2020. View Source

Gellerman thanked the many individuals and foundations whose gifts to the 501(c)(3) nonprofit organization support NETRF’s research and educational activities. A generous gift from the Margie and Robert E. Petersen Foundation will fund several of the new projects. Additional support has been provided by the Goldhirsh-Yellin Foundation of Los Angeles and Advanced Accelerator Applications.