On June 21, 2018 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported that it has dosed its first patient as part of its Phase 1/2 immuno-oncology trial in patients with newly diagnosed glioblastoma (GBM) (Press release, Inovio, JUN 21, 2018, View Source [SID1234527415]). The efficacy trial is designed to evaluate Inovio’s INO-5401 T cell activating immunotherapy encoding multiple antigens expressed by GBM and INO-9012, an immune activator encoding IL-12, in combination with cemiplimab (REGN2810), a PD-1 inhibitor developed by Regeneron Pharmaceuticals.

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Dr. J. Joseph Kim, Inovio’s President and Chief Executive Officer, said, "GBM is a devastating cancer, and malignant glioma has already claimed the lives of Senator Ted Kennedy and Beau Biden, the son of the former Vice President Joe Biden. GBM is also the cancer that Senator John McCain and thousands of other patients are battling every year. We are proud to have treated our first patient with a powerful combination of Inovio’s T cell-generating immunotherapy INO-5401 with Regeneron’s PD-1 checkpoint inhibitor this week. This is an important step for Inovio’s plan to use its T cell-generating therapies in combination with PD-1/PD-L1 inhibitors for GBM and for multiple other cancers to improve overall efficacy. In preclinical studies, combination of Inovio’s T cell-generating immunotherapies along with checkpoint inhibitors have shown to shrink tumors and improve overall survival of tumor-bearing animals. In this GBM trial, our goal is to increase the overall survival of patients facing a disease where neither the standard of care, nor clinical outcomes have not changed in a clinically significant way in more than a decade."

Dr. David Reardon, Associate Professor, Medicine, Harvard Medical School and Clinical Director, Center for Neuro-Oncology, Medical Oncology, Dana-Farber Cancer Institute and the trial’s coordinating principal investigator, said, "The Inovio vaccine platform is highly innovative and uniquely designed with the potential to generate robust anti-tumor immune responses. We are very hopeful that this novel vaccine technology will translate into meaningful therapeutic benefit when integrated with standard radiation and temozolomide chemotherapy combined with anti-PD-1 treatment for newly diagnosed glioblastoma patients in our recently initiated trial."

Inovio holds clinical partnerships with MedImmune for INO-3112 (MEDI0457) (in HPV-related cancers) and collaborations, with Roche/Genentech and Regeneron for INO-5401 (in bladder cancer and GBM), each providing for clinical evaluation of Inovio immunotherapies combined with checkpoint inhibitors. In particular, the INO-5401 collaborations are based on a strong scientific rationale to combine two immunotherapies: INO-5401, which generates antigen-specific killer T cells, and a checkpoint inhibitor, which augments T cell activity.

The open-label trial of 50 newly diagnosed GBM patients will be conducted at approximately 25 U.S. sites, and the primary endpoint is safety and tolerability. The study will also evaluate immunological impact, progression-free survival and overall survival.

About Glioblastoma

Glioblastoma (GBM) is the most common and aggressive type of brain cancer and remains a devastating disease for both patients and caregivers. Its prognosis is extremely poor, despite a limited number of new therapies approved over the last 10 years. The median overall survival for patients receiving standard of care therapy is approximately 15 months and the average five-year survival rate is less than five percent.

About INO-5401

INO-5401 includes Inovio’s SynCon antigens for hTERT, WT1, and PSMA, and has the potential to be a powerful cancer immunotherapy in combination with checkpoint inhibitors. The National Cancer Institute previously highlighted hTERT, WT1, and PSMA among a list of important cancer antigens, designating them as high priorities for cancer immunotherapy development. These three antigens are known to be over-expressed, and often mutated, in a variety of human cancers, and targeting these antigens may prove efficacious in the treatment of patients with cancer.

On June 21, 2018 Blueprint Medicines Corporation (NASDAQ: BPMC), a leader in discovering and developing targeted kinase medicines for patients with genomically defined diseases, reported it has dosed the first patient in the VOYAGER Phase 3 clinical trial, which is evaluating the safety and efficacy of avapritinib compared to regorafenib in patients with advanced gastrointestinal stromal tumors (GIST) (Press release, Blueprint Medicines, JUN 21, 2018, View Source;p=RssLanding&cat=news&id=2355440 [SID1234527414]). The VOYAGER trial is designed to enroll patients previously treated with imatinib and one or two additional tyrosine kinase inhibitors (TKIs).

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"The initiation of the VOYAGER Phase 3 trial represents an important milestone for Blueprint Medicines, as we advance efforts to achieve registration of avapritinib in a broad GIST population," said Andy Boral, M.D., Ph.D., Chief Medical Officer of Blueprint Medicines. "With compelling Phase 1 clinical data showing objective responses and prolonged progression free survival in heavily pretreated patients, we believe avapritinib has the potential to offer improved disease control to patients with third-line and later advanced GIST."

Avapritinib is a potent and selective inhibitor of activated KIT and PDGFRA mutant kinases. TKIs currently approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced GIST only bind to the inactive conformations of KIT and PDGFRA, whereas avapritinib is uniquely designed to bind and inhibit the active conformation of these protein kinases. This allows for potent inhibition of both primary and secondary mutations that shift the kinase towards its active conformation. In patients with relapsed metastatic GIST whose disease has progressed following treatment with imatinib, resistance mutations in the activation loop accumulate with higher frequency, limiting the effectiveness of approved TKIs.

About the VOYAGER Phase 3 Clinical Trial

The VOYAGER clinical trial is a global, open-label, randomized, Phase 3 trial designed to evaluate the safety and efficacy of avapritinib versus regorafenib in patients with third- or fourth-line advanced GIST. Eligible patients will have previously received imatinib and one or two additional tyrosine kinase inhibitors. The trial is designed to enroll approximately 460 patients randomized 1:1 to receive avapritinib dosed at 300 mg once daily (QD) or regorafenib dosed at 160 mg QD for three weeks, followed by one week off, at multiple sites in the United States, European Union, Australia and Asia. Patients who are randomized to receive regorafenib and experience disease progression confirmed by central radiology review may be offered the opportunity to cross-over to the avapritinib treatment arm. The primary efficacy endpoint is progression free survival determined by central radiologic assessment per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Secondary endpoints include objective response rate, overall survival and quality of life outcome measures. Regorafenib, also known as Stivarga, is an oral, multi-kinase inhibitor approved by the U.S. Food and Drug Administration for the treatment of patients with third-line GIST.

Patients and physicians interested in the VOYAGER Phase 3 trial can contact the Blueprint Medicines study director at [email protected] or 1-617-714-6707. For more information about the VOYAGER trial, please visit www.voyagertrial.com. Additional details are also available on www.clinicaltrials.gov (ClinicalTrials.gov Identifier: NCT03465722).

About Avapritinib

Avapritinib is an orally available, potent and highly selective inhibitor of KIT and PDGFRA. In certain diseases, a spectrum of clinically relevant mutations forces the KIT or PDGFRA protein kinases into an increasingly active state. Avapritinib is uniquely designed to bind and inhibit the active conformation of these proteins, including PDGFRα D842V and KIT D816V at sub-nanomolar potency. Blueprint Medicines is initially developing avapritinib, an investigational medicine, for the treatment of patients with advanced GIST and systemic mastocytosis.

In June 2017, avapritinib received Breakthrough Therapy Designation from the FDA for the treatment of patients with unresectable or metastatic GIST harboring the PDGFRα D842V mutation. Previously, the FDA granted orphan drug designation to avapritinib for GIST and mastocytosis and fast track designation to avapritinib for GIST. In addition, the European Commission has granted orphan drug designation to avapritinib for GIST. In May 2018, Blueprint Medicines announced plans to submit a New Drug Application to the FDA for avapritinib for the treatment of PDGFRα D842V-driven GIST in the first half of 2019. In June 2018, Blueprint Medicines announced an exclusive collaboration and license agreement with CStone Pharmaceuticals for the development and commercialization of avapritinib and certain other drug candidates in Mainland China, Hong Kong, Macau and Taiwan.

About GIST

GIST is a sarcoma, or tumor of bone or connective tissue, of the gastrointestinal (GI) tract. Tumors arise from cells in the wall of the GI tract and occur most often in the stomach or small intestine. Most patients are diagnosed between the ages of 50-80, and diagnosis is typically triggered by GI bleeding, incidental findings during surgery or imaging and, in rare cases, tumor rupture or GI obstruction.

Most GIST cases are caused by a spectrum of clinically relevant mutations that force the KIT or PDGFRA protein kinases into an increasingly active state. In addition, resistance mutations in the activation loop accumulate with higher frequency in heavily pretreated patients. Because currently available therapies only bind to the inactive protein conformations, certain primary and secondary mutations typically lead to treatment resistance and disease progression.

Treatment options for KIT-driven GIST patients whose disease progresses or develops resistance are currently limited, with approved therapies providing a progression free survival of up to six months and a response rate between five percent and seven percent. There are no effective treatment options for patients with PDGFRα D842V-driven GIST, and progression often occurs in as little as three months with available treatment options.

On June 21, 2018 MetaStat, Inc. (OTCQB: MTST), a precision medicine company developing novel anti-metastatic medications for patients with aggressive cancer, reported that positive results from preclinical studies showing treatment with MAPKAPK2 kinase inhibitors reverse MENA-driven aggressive tumor cell phenotypes and significantly reduce metastasis at the Cancer Dormancy and Residual Disease meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in Montreal, Quebec on June 20, 2018 (Press release, MetaStat, JUN 21, 2018, https://ir.stockpr.com/metastat/company-news/detail/399/metastat-presents-positive-data-showing-inhibition-of-the-mena-pathway-reduces-cancer-cell-dissemination-and-paclitaxel-resistance-in-aggressive-cancer [SID1234527413]).

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"Until recently, the MENA pathway was considered to be an undruggable target. These results show inhibition of the MENA pathway and reversal of MENA-dependent phenotypes are possible by targeting MAPKAPK2," stated Douglas A. Hamilton, MetaStat’s President and CEO. "We are leveraging a proven and highly successful therapeutic strategy in oncology to develop proprietary first-in-class MAPKAPK2 kinase inhibitors."

MetaStat reported MENA-induced fibronectin remodeling, tumor cell adhesion and invasion were reversed to MENA-null levels when treated with MAPKAPK2 inhibitors in vitro. MAPKAPK2 inhibitor monotherapy reduced lung metastasis similar to the previously published effects of MENA deficiency in the MMTV-PyMT murine model. Significant decreases in the number of animals with any detectable circulating tumor cells (CTCs) following treatment were reported in the MDA-MB-231 human metastatic triple negative breast cancer model. Further, in contrast to paclitaxel monotherapy, treatment with the MAPKAPK2 inhibitor alone or in combination with paclitaxel significantly reduced the growth rate of MMTV-PyMT primary tumors and the development of lung metastasis.

On June 20, 2018 SillaJen, Inc., (KOSDAQ:215600), a clinical-stage, biotherapeutics company focused on the development of oncolytic immunotherapy products for cancer, reported the first patient has been enrolled in REN026, the Phase 1b clinical trial of Pexa-Vec (pexastimogene devacirepvec) in combination with cemiplimab (REGN2810) for the treatment of renal cell cancer (RCC) (Press release, SillaJen, JUN 20, 2018, View Source [SID1234527430]). The first patient was enrolled in the United States, with expansion to sites in South Korea and Australia anticipated over the coming weeks.

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SillaJen is collaborating with Regeneron to evaluate Pexa-Vec, SillaJen’s lead clinical candidate, in combination with Regeneron’s cemiplimab, an anti-PD1 monoclonal antibody. The aim of the trial is to assess the safety and efficacy of the combination in patients with unresectable or metastatic renal cell carcinoma. The study will also investigate the immune modulating potential of Pexa-Vec given concurrently with checkpoint inhibitor therapy by evaluating multiple blood and tissue biomarkers.

"Given the initial activity seen with Pexa-Vec monotherapy and the potential of oncolytic viruses to enhance anti-tumor immunity, combining Pexa-Vec with cemiplimab is quite rational and has the promise to build upon the activity of checkpoint inhibitor therapy alone in RCC. This trial will not only assess the clinical activity of the two agents but allow us to assess in more depth the changes elicited in anti-tumor immunity following treatment by examining peripheral blood and tumor samples. This will give us proof of concept data that will help us expand this approach to other tumor types," stated James Burke, M.D., chief medical officer at SillaJen.

About Pexa-Vec and the SOLVE Platform
Pexa-Vec is the most advanced product candidate from SillaJen’s proprietary SOLVE (Selective Oncolytic Vaccinia Engineering) platform. The vaccinia strain backbone of Pexa-Vec has been used safely in millions of people as part of a worldwide vaccination program, and over 300 cancer patients have been treated with Pexa-Vec to date. Pexa-Vec was engineered to target common genetic defects in cancer cells by deleting their thymidine kinase (TK) gene, thus making Pexa-Vec dependent on the cellular TK expressed at persistently high levels in cancer cells. Pexa-Vec is also engineered to express granulocyte-macrophage colony stimulating factor (GM-CSF) protein. GM-CSF complements the cancer cell lysis of the product candidate, leading to a cascade of events resulting in tumor necrosis, tumor vasculature shutdown and sustained anti-tumoral immune attack. Pexa-Vec has been shown to be effective when delivered both intratumorally and systemically by intravenous administration. Pexastimogene devacirepvec (Pexa-Vec) is currently being evaluated in a worldwide Phase 3 clinical trial for advanced primary liver cancer, and more information can be found at: View Source

On June 20, 2018 AIVITA Biomedical, a biotech company specializing in innovative stem cell applications, reported the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug (IND) application for a Phase II clinical trial investigating the Company’s ROOT OF CANCER technology in patients with glioblastoma multiforme (Press release, AIVITA Biomedical, JUN 20, 2018, View Source [SID1234527425]). This will be the third investigation of AIVITA’s platform cancer immunotherapy, which is currently the subject of a Phase II clinical trial in ovarian cancer in the USA, and a commercialization effort in melanoma in Japan.

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AIVITA’s single-arm, open-label trial calls for approximately 55 patients with newly diagnosed glioblastoma multiforme to be enrolled with the intent to receive the Company’s ROOT OF CANCER treatment. The treatment consists of the patient’s own dendritic cells loaded with tumor antigens from the patient’s own tumor-initiating cells. The treatment will be administered in a series of injections along with standard care, which may include surgery, chemotherapy and radiation, as well as checkpoint inhibitors should they eventually be approved as standard care.

"We are delighted with this opportunity to help glioblastoma multiforme patients, who face the most aggressive form of brain cancer," said Dr. Hans Keirstead, AIVITA’s Chief Executive Officer. "This approval reflects the platform nature, the safety and the manufacturing efficiency of our novel technology."

The University of California, Irvine will be the study’s first site, with additional sites to follow.

About Glioblastoma Multiforme

Glioblastoma Multiforme is the most aggressive and most common form of malignant brain tumor. Median survival is only nine months, rising to 15–16 months for those receiving standard of care surgery and adjuvant chemoradiation.1 The cause of most cases is unclear. The National Cancer Institute estimates there will be 23,880 new cases of brain and nervous system cancer in 2018.

[1] Bi, Wenya Linda, and Rameen Beroukhim. "Beating the Odds: Extreme Long-Term Survival with Glioblastoma." Neuro-Oncology 16.9 (2014): 1159–1160. PMC. Web. 18 June 2018.
About the ROOT OF CANCER GBM trial

AIVITA’s treatment is a platform technology applicable to most solid tumor types and consists of autologous dendritic cells loaded with autologous tumor antigens from autologous self-renewing tumor-initiating cells.

Patients eligible for treatment will be those (1) who have recovered from surgery such that they are about to begin concurrent chemotherapy and radiation therapy (CT/RT), (2) for whom an autologous tumor cell line has been established, (3) have a KPS of > 70, and (4) have undergone successful leukapheresis from which peripheral blood mononuclear cells (PBMC) were obtained that can be used to generate dendritic cells (DC).

For additional information about AIVITA’s AV-GBM-1 trial please visit: View Source