On June 27, 2018 Sarah Cannon Research Institute – UK, Part of HCA Healthcare UK, reported the European initiation of a Phase II clinical trial studying the effectiveness of TIL therapy in the treatment of patients facing metastatic melanoma (Press release, Sarah Cannon Research Institute, JUN 27, 2018, View Source [SID1234527503]). Sarah Cannon is the first clinical site in Europe to treat a patient on this trial.

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Sarah Cannon Research Institute – UK, which provides access to clinical trials to both private and NHS cancer patients, is one of 25 centres around the world taking part in Iovance Biotherapeutics’ Phase II TIL trial. The patient population participating in the trial will include people with late-stage melanoma where prior treatments have proven ineffective. The initiation of this trial took place at HCA Healthcare UK at University College Hospital, a complex cancer facility in London.

"We are pleased to offer this cutting-edge immunotherapy option for patients facing melanoma throughout Europe," said Carol Woodward, Vice President of Sarah Cannon Development Innovations and European Operations. "Through Sarah Cannon Research Institute – UK, Part of HCA Healthcare UK, we can ensure patients have access to the latest treatments in their cancer journey."

TIL therapy is a procedure in which white blood cells that have left the bloodstream and migrated towards a tumour, TIL (tumour infiltrating lymphocytes), are enriched to help fight and reduce cancers. As part of the therapy, TIL cells are extracted from a patient’s tumour, amplified in a laboratory to increase their number, and then infused back into the patient. At the recent 2018 ASCO (Free ASCO Whitepaper) Annual Meeting, research for TIL therapy in abstract TPS9595, indicated the potential for durable and complete responses, even in heavily pre-treated patients.

"We are excited to offer this therapy to melanoma patients seeking the latest options," said Hendrik-Tobias Arkenau, MD, PhD, FRCP, Executive Medical Director of the Drug Development Program, Sarah Cannon Research Institute – UK. "TIL therapy is an innovative treatment that brings together a multidisciplinary team to provide patients with access to a complex and cutting-edge treatment approach."

For more information, contact [email protected] / 020 7025 1363 / 07876 899 925

On June 27, 2018 Purdue Pharma L.P. reported successful completion of a first-in-human Phase 1 dose escalation study of tinostamustine in patients with relapsed or refractory hematological malignancies for which there are no available therapies (Press release, Purdue Pharma, JUN 27, 2018, View Source [SID1234527497]). The study evaluated the safety and pharmacokinetics, and sought to determine the maximum tolerated dose and inform a Phase 2 dose of tinostamustine. 1

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The multi-acting therapy candidate tinostamustine, previously known as EDO-S101, is a novel and potentially first-in-class alkylating deacetylase inhibitor (AK-DACi) therapy being studied for its potential to improve access to the DNA strands within cancer cells, break them, and counteract the cancer cells’ attempt to repair the DNA damage. It is in development for a range of rare or difficult to treat blood cancers and solid tumors. Based on the results of this Phase I human trial, Purdue will support advancement of tinostamustine into further clinical studies.

"We are pleased with the outcome of this promising early stage oncology program and we believe it has the potential to make meaningful clinical contributions in areas with significant unmet needs," said Craig Landau, MD, president and CEO, Purdue Pharma. "In addition to our established commitments in oncology and neuroscience, we are actively seeking opportunities to collaborate across a number of therapeutic areas as part of our ongoing efforts to diversify our scientific research and bring therapies to market that may improve outcomes for patients."

The reported completion of this study is the first clinical update since Purdue announced in November 2017 significant oncology-related investments to establish a portfolio of drug candidates with the potential to deliver new cancer therapies, in areas of high unmet medical need, to physicians and patients. As part of these investments, Purdue is currently supporting research for four drug candidates across 14 different cancer types. Research on these compounds is being advanced on behalf of Purdue by Mundipharma EDO.

In addition to tinostamustine, Purdue’s clinical stage oncology portfolio includes etoposide toniribate, a novel target-activated topoisomerase inhibitor that delivers the chemotherapy etoposide to tumors in an inactive form where it is ‘switched on’ by enzymes called carboxylesterases. Purdue also has two late pre-clinical stage antibody-drug conjugates, EDO-B776 and EDO-B278, in development. EDO-B776 is being studied for its potential to target the cancer antigen 125 (CA-125) in ovarian cancer. EDO-B278, which targets human tissue factor, is in development for treatment of various solid tumors.

The decision to move tinostamustine into Phase 1 human trials was supported by preclinical studies, which suggest that tinostamustine may deliver both alkylating activity and pan-histone deacetylase (HDAC) inhibition to improve access to the DNA strands within cancer cells, break them, and counteract the cancer cells’ attempt to repair the DNA damage.

Purdue will also continue to selectively seek additional oncology product assets through licensing and acquisition, and the company will maintain a priority interest in candidates with mechanisms complementary to emerging immuno-oncology based treatment paradigms

On June 27, 2018 Pfizer Inc. (NYSE:PFE) reported that the U.S. Food and Drug Administration (FDA) accepted the company’s New Drug Application and granted Priority Review designation for glasdegib, an investigational oral smoothened (SMO) inhibitor, being evaluated for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) in combination with low-dose cytarabine (LDAC), a type of chemotherapy (Press release, Pfizer, JUN 27, 2018, View Source [SID1234527490]).

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"Patients with acute myeloid leukemia who are ineligible for intensive chemotherapy are in critical need of new treatment options to improve their overall survival," said Mace Rothenberg, M.D., chief development officer, Oncology, Pfizer Global Product Development. "In an investigational Phase 2 study, glasdegib in combination with low-dose cytarabine showed a significant improvement in overall survival compared to patients who received low-dose cytarabine alone. Glasdegib is the first smoothened inhibitor to potentially offer such a benefit to patients with acute myeloid leukemia, and we are proud that our application was accepted by the FDA for Priority Review."

The FDA grants Priority Review designation to medicines that may offer significant advances in treatment or may provide a treatment where no adequate therapy exists. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is in December 2018.

The submission is based on results from the Phase 2 BRIGHT 1003 study, a randomized, open-label, multicenter trial investigating glasdegib combined with LDAC (n=88) versus LDAC alone (n=44) in 132 patients with previously untreated AML or high-risk myelodysplastic syndrome (MDS) who were not eligible for intensive chemotherapy. Results demonstrated a significant improvement in the primary endpoint of overall survival (OS). Median OS was 8.8 months for patients treated with glasdegib plus LDAC compared with 4.9 months for patients treated with LDAC only. This difference represented a 49.9 percent reduction in the risk of death for patients treated with glasdegib plus LDAC (HR: 0.501, 95% CI: 0.334, 0.752, one-sided p-value 0.0003). The BRIGHT 1003 results were presented in 2016 at the 58th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

The most frequently (≥30% of patients) reported adverse events (AEs) in patients treated with glasdegib plus LDAC compared to LDAC alone were anemia (45% vs 42%), febrile neutropenia (36% vs 27%), nausea (36% vs 12%), decreased appetite (32% vs 12%), fatigue (31% vs 20%) and thrombocytopenia (30% vs 27%). The most frequently (≥15% of patients) reported serious AEs for patients treated with glasdegib plus LDAC compared to LDAC alone were febrile neutropenia (29% vs 20%) and pneumonia (21% vs 17%).

About Glasdegib

Glasdegib is an investigational, oral, once-daily therapy that is thought to inhibit the SMO receptor, thereby disrupting the Hedgehog pathway. Abnormal Hedgehog pathway activation is thought to play a role in the development of multiple types of cancers, including solid tumors and hematologic malignancies. It has not received regulatory approval in any country.

The Phase 3 BRIGHT AML 1019 trial (NCT03416179), which is evaluating the addition of glasdegib to intensive or non-intensive chemotherapy in patients with newly diagnosed AML, began enrolling earlier this year.

About Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults and accounts for approximately 80 percent of all cases of acute leukemia.1 An estimated 19,520 people are expected to be diagnosed with AML in the U.S. in 2018.1 Despite recent advancements, only approximately one in four patients with AML survive longer than five years, and additional treatment options are needed to reduce incidence of disease progression and relapse.2,3 This is especially true for patients who are unable to receive intensive chemotherapy and are triaged to other treatments associated with poorer outcomes.

On June 28, 2018 argenx (Euronext & Nasdaq: ARGX), a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, reported the achievement of the second of two preclinical milestones towards an investigational new drug (IND) filing for ARGX-115, triggering a further $ 10 million payment from AbbVie (Press release, argenx, JUN 28, 2018, View Source;p=RssLanding&cat=news&id=2356311 [SID1234527488]).

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In April 2016, argenx entered into a development and exclusive license option agreement with AbbVie to develop and commercialize ARGX-115. Under the terms of that agreement, argenx has been responsible for conducting and funding all ARGX-115 research and development activities up to completion of IND-enabling studies.

Over the course of the past two years, argenx has been eligible to receive two preclinical milestones of $ 10 million each. The second milestone was achieved today.

About ARGX-115
ARGX-115 employs argenx’s SIMPLE Antibody(TM) technology and binds specifically to the protein glycoprotein A repetitions predominant (GARP), which plays a key role in the regulation of production and release of active transforming growth factor beta (TGF-beta). ARGX-115 is believed to selectively limit the immunosuppressive activity of activated regulatory T-cells (Tregs), thereby stimulating the immune system to attack cancer cells. While the normal function of Tregs is to suppress certain compartments of the immune system to prevent self-directed immune responses through the release of active TGF-beta, Tregs can also prevent the immune system from recognizing and suppressing pathogenic cells including cancer cells. We believe the selective inhibition of TGF-beta release by Tregs is potentially superior to systemic inhibition of TGF-beta activity or depletion of Tregs and may give rise to therapeutic products with an improved safety profile.

ARGX-115 was discovered under argenx’s Innovative Access Program with the de Duve Institute / Université Catholique de Louvain / WELBIO and exclusively licensed under a research and option agreement in 2013.

On June 27, 2018 Kangpu Biopharmaceuticals, Ltd., a clinical-stage company based in Shanghai, China, reported that a phase I, multi-center, open-label study to evaluate the safety, tolerability, pharmacokinetics and preliminary evidence of antitumor activity of KPG-121 in combination with Enzalutamide in adult subjects with metastatic castration-resistant prostate cancer (mCRPC) has been launched in the United States (Press release, Kangpu Biopharmaceuticals, JUN 27, 2018, View Source [SID1234527486]). The study takes place at 3 medical centers in the US; part of Accelovance’s network of HERO sites dedicated to early phase research in oncology. Specifics of the study can be found on www.clinicaltrials.gov/NCT03569280.

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About KPG-121
KPG-121 is a novel generation of Lenalidomide. Compared with Lenalidomide, KPG-121 has shown enhanced immunomodulatory activities and improved anti-angiogenic properties in the preclinical studies. Results from in vitro assays and in vivo studies of mCRPC animal xenograft models demonstrated that better efficacy was observed for KPG-121 compared to Lenalidomide, when combined with Enzalutamide, Abiraterone Acetate, Apalutamide or Darolutamide. In the combination studies with Enzalutamide, KPG-121 significantly improved anti-tumor efficacy when compared to Enzalutamide alone.