On February 24, 2016 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new cancer immunotherapies, reported that, following the successful completion of the initial dose cohort, the first patient has been dosed at the succeeding dose level in the Company’s ongoing multicenter Phase 1 study of Ad-RTS-hIL-12 + orally administered veledimex in recurrent or progressive glioblastoma or grade III malignant glioma (Press release, Ziopharm, FEB 24, 2016, View Source [SID:1234509172]). Ad-RTS-hIL-12 + veledimex is a novel viral gene therapy candidate for the controlled expression of IL-12, a critical protein for stimulating an anti-cancer T-cell immune response.

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"This Phase 1 study of Ad-RTS-hIL-12 + veledimex is notable as it is among only a handful of multi-center gene therapy studies ever conducted, involves treatment directly in the brain tumor and addresses an advanced stage of disease where survival outcomes are often dire," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "We are encouraged by the clinical observations to date and look forward to identifying the optimal dose as we continue to enroll additional patients in the trial."

Dr. Lebel added: "Advanced brain cancer is a disease for which there are far too few treatment options. We look forward to presenting follow-up data from this study mid-year, and exploring additional therapy combinations in the clinic starting this year, including the addition of a checkpoint inhibitor to Ad-RTS-IL-12 + veledimex."

At the Society for Neuro-Oncology 20th Annual Scientific Meeting in November 2015, and in subsequent presentations, the Company announced results, including encouraging activity and "on-target toxicity," as well as evidence that veledimex crosses the blood brain barrier, from the first cohort in the study at a dosing regimen of Ad-RTS-hIL-12 2.0×10^11 + veledimex 20mg/day. After a review of tolerability data from this cohort of seven patients by a panel of independent neuro oncology experts, convened as the Data Safety Monitoring Board for the trial, the next dosing cohort of veledimex (40mg/day) was approved.

The ongoing multi-center Phase 1 trial of Ad-RTS-hIL-12 + veledimex examines a gene therapy strategy for recurrent high-grade gliomas, with the goal of generating a localized anti-tumor immune response. The primary objective of the study is to determine the safety and tolerability of a single intra-tumoral Ad-RTS-hIL-12 injection activated upon dosing with oral veledimex. Secondary objectives are to determine the Ad-RTS-hIL-12 + veledimex maximum tolerated dose, the immune responses elicited by Ad-RTS-hIL-12 + veledimex, and assessment of biologic response. The Company anticipates reporting updated results from the study at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in June 2016 and preclinical results combining Ad-RTS-hIL-12 + veledimex and checkpoint inhibitors at the American Society of Gene and Cell Therapy Annual Meeting in May 2016.

On February 24, 2016 Asterias Biotherapeutics, Inc. (NYSE:AST) reported the successful completion of an End-of-Phase 2 meeting with the U.S. Food and Drug Administration (FDA) for AST-VAC1, its investigational therapy targeting acute myeloid leukemia (AML) (Press release, BioTime, FEB 24, 2016, View Source [SID:1234509171]).

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During the meeting, the FDA indicated general agreement with Asterias’ proposed development plan for registration of AST-VAC1 through a single Phase 3 trial to support an accelerated development pathway and Biologics License Application (BLA) filing. In this study, Asterias will assess the impact of AST-VAC1 compared to placebo on the duration of relapse-free-survival as the primary endpoint, and on overall survival as the secondary endpoint in patients who have achieved complete remission using standard therapies. The proposed trial will include AML patients 60 years and older, along with younger individuals who are at high risk for relapse and are not candidates for allogeneic bone marrow transplantation. Pending positive results, this trial could be the basis for accelerated approval of AST-VAC1. Asterias currently plans to submit a request for a Special Protocol Assessment (SPA) to the FDA to confirm the primary endpoint and other design elements of this pivotal Phase 3 trial.

"We are very pleased with the outcome of the End-of-Phase 2 meeting and the feedback from our discussion with the FDA," stated Pedro Lichtinger, President and Chief Executive Officer. "We believe the results from the Phase 2 clinical trial of AST-VAC1 in AML are encouraging. We appreciate the valuable guidance that the FDA has provided us regarding the design and conduct of a Phase 3 registration program and look forward to further discussions in the Special Protocol Assessment process."

About Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. AML is the most common type of acute leukemia and has the potential for rapid progression, if untreated. In AML, the bone marrow produces an excess number of immature cells known as blasts. In AML, these blasts fail to mature into normal red and white blood cells. Instead, the blasts proliferate and accumulate in the bone marrow and peripheral blood, leading to deficiencies in normal mature cells. These deficiencies, often referred to as cytopenias, can induce several adverse effects including anemias and susceptibility to infections. Current treatment strategies for AML are associated with significant morbidities and in most instances, AML leads to death.

Approximately 20,500 new cases of AML are diagnosed in the U.S. annually. AML remains a high unmet clinical need, particularly in patients over the age of 60 years who face poor outcomes and have limited therapeutic options. Treatment and prognosis in AML is strongly influenced by a patient’s age and tumor profile. Successful treatment and survival of advanced age patients or those with a high risk profile is very poor, with a four year relapse-free survival of 10% – 20% (Rolig et al, 2011). Detailed characterizations of genetic abnormalities associated with AML have elucidated their high number and relative complexity, making development of targeted therapeutics to these mutations very challenging. For this reason, broad immunotherapy approaches such as autologous cell vaccines are particularly promising.

About AST-VAC1

AST-VAC1 is a cancer immunotherapy, consisting of autologous mature antigen-presenting dendritic cells pulsed with a messenger RNA for the protein component of human telomerase (hTERT) and a portion of a lysosomal targeting signal (LAMP). hTERT is a common protein in tumor cells and is responsible for the increased proliferative lifespan of cancer cells. In AST-VAC1, the dendritic cells present telomerase to the immune system to induce T cells to target and kill hTERT-expressing tumor cells. The LAMP signal allows AST-VAC1 to stimulate both cytotoxic and helper T cell responses to telomerase, critical elements to induce and maintain immune responses that kill tumor cells. In June 2015, Asterias announced long-term follow-up results from a Phase 2 clinical trial in AML patients receiving AST-VAC1. In this trial, twenty-one patients received at least three injections of AST-VAC1, including 19 patients in complete remission (CR). AST-VAC1 showed a strong safety profile in this trial and in a previous study in prostate cancer patients. Eleven of the 19 patients (58 percent) in the trial remain in CR with a median duration of follow-up of 52 months from first vaccination. Four of the seven patients who were at least 60 years old at the time of immunotherapy with AST-VAC1 remained relapse-free 52 to 59 months from first vaccination.

Because of the widespread expression of telomerase in the majority of cancers, AST-VAC1 is a platform immunotherapeutic that could be used alone or in conjunction with other therapeutics such as immune checkpoint inhibitors to target immune-based destruction of tumors.

About Accelerated Approval

The FDA instituted its Accelerated Approval Program to allow for earlier approval of drugs that treat serious conditions, and that fill an unmet medical need based on a surrogate endpoint. A surrogate endpoint is a marker, such as a laboratory measurement, radiographic image, physical sign or other measure that is thought to predict clinical benefit, but is not itself a measure of clinical benefit. The use of a surrogate endpoint can considerably shorten the time required prior to receiving FDA approval.

Drug companies are still required to conduct studies to confirm the anticipated clinical benefit. These studies are known as Phase 4 confirmatory trials. If the confirmatory trial shows that the drug actually provides a clinical benefit, then the FDA grants traditional approval for the drug. If the confirmatory trial does not show that the drug provides clinical benefit, FDA has regulatory procedures in place that could lead to removing the drug from the market.

On February 24, 2016 Cancer Research UK’s Centre for Drug Development (CDD), in partnership with Amgen Inc., reported that they have launched a new clinical trial to test a drug that could stop a patient’s immune system from protecting tumours (Press release, Cancer Research UK, FEB 24, 2016, http://www.cancerresearchuk.org/about-us/cancer-news/press-release/2016-02-24-cancer-research-uk-launches-trial-for-potential-new-drug-that-could-help-immune-system-fight-cancer [SID:1234509157]).

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Cancer Research UK scientists are studying Amgen’s experimental cancer drug , called AMG319, to find out if it removes the defence shield that hides cancer cells from the immune system. It targets a protein called PI3K delta leading to destruction of the cancer cells when tested in the laboratory.

The Phase II trial, taking place at Poole Hospital, Southampton General Hospital, and the Clatterbridge Cancer Centre/Aintree University Hospital, looks at the effects of giving this drug to patients with a type of head and neck cancer known as squamous cell carcinoma (HNSCC), to determine whether it affects their immune response.

There will be around 54 patients with HPV-negative* HNSCC of the lower and upper parts of the throat (hypopharynx and oropharynx) or mouth in the study. Patients will be randomly assigned to receive either AMG319 or a placebo, during the regular break from treatment to avoid disruption to a patient’s care.

It is the 10th treatment to enter Cancer Research UK’s Clinical Development Partnerships (CDP) scheme.
CDP is a joint initiative between Cancer Research UK’s CDD and Cancer Research Technology, aiming to increase the number of cancer clinical trials and to progress promising anti-cancer agents by working in partnership with pharmaceutical companies.

Professor Christian Ottensmeier, trial lead from the University of Southampton and the Southampton Experimental Cancer Medicine Centre, said: "This is a really exciting trial because we’re using this drug in solid tumours for the first time. It also tries a whole new concept of cancer therapy in solid cancers for the first time. We hope that after taking the drug, patients will have more cancer fighting immune cells in their tumour. We will study in detail how the immune cells behave before and after AMG319 and whether they have become more effective."

Dr Emma King, clinical lead at the Poole Hospital, said: "I am really pleased that this trial gives our head and neck cancer patients and opportunity to get this new drug."

Tony Hoos, Vice president of Medical, Europe at Amgen, said: "The intersection of immunology and oncology represents one of the most promising approaches which may have a significant impact for patients with cancer today.

"We value the work that Cancer Research UK has done to make it possible to develop this promising drug to the next stage. This new trial will give us a better understanding of how AMG319 works, helping us learn more about its potential in patients who might benefit."

Dr Nigel Blackburn, Cancer Research UK’s director of drug development, said: "We’re delighted that the collaboration between Amgen and our Centre for Drug Development is moving into Phase II trials. It means we’re getting closer to providing a new treatment for cancer patients.

"Teaching the body’s immune system to fight cancer is a promising area of cancer research and we’re excited to see how this drug may help."