Immunovative Inc. Announces Regulatory Clearance to Conduct a Phase II/III Clinical Trial in Advanced Metastatic Breast Cancer for AlloStim
Published: Nov 29, 2012
LOS ANGELES, CA--(Marketwire - November 29, 2012) -
ITL announced on November 26, 2012 that it had successfully completed upgrades to its state-of-the-art Jerusalem GMP cell manufacturing facility and its GMP operations in order to comply with the anticipated increased demand and higher level of GMP compliance requirements of advanced clinical trials and that an Investigational New Drug ("IND") application seeking regulatory clearance to launch a large, randomized, Phase II/III clinical trial in metastatic breast cancer was pending with the Thai Ministry of Public Health ("Thai FDA") and with the National Ethics Committee of Thailand ("National EC") and the Ethics Committee of the National Cancer Institute of Thailand ("Local EC"). ITL today announces that it has been notified by Thai FDA, the National EC and Local EC that our Thai IND application and our Phase II/III metastatic breast cancer clinical trial has been approved for subject accrual. An additional IND application has been submitted to the same agencies seeking clearance to initiate a Phase I/II clinical study of our AlloVax™ product candidate in refractory head and neck cancer. This application is currently pending.
The Phase II/III clinical trial is a dual arm, randomized, placebo-controlled, double blind (investigators and subjects will not know if they receive AlloStim™ or a placebo) study in patients with metastatic breast cancer previously treated with an anthracycline, taxane and capecitabine (xeloda). Her2+ patients must have additionally failed a trastuzumab (Herceptin)-containing regimen and pre-menopausal ER+ and/or PR+ patients must be resistant to endocrine therapy (including an aromatase-inhibitor). A total of 208 subjects will be accrued (104 in each arm). The randomization scheme is designed to provide equal representation as to age, Her2+ status and triple negative status in each of the arms. The primary end-point of the trial is over-all survival. Secondary end-points include extensive safety analysis and evaluation of RECIST in correlation with pathological examination of longitudinal biopsy samples. Tertiary end-points include exploratory immunological response monitoring and determination of whether survival or response correlates to neo-antigen and/or recall antigen immune competence.
The trial is expected to complete accrual in approximately two years. It is expected that another year of follow-up may be required to have a chance for the survival data to mature and to possibly reach statistical significance. The trial has been powered at 80% to be able to detect a 50% or greater difference in over-all survival between the treatment and placebo arms (two-tailed alpha of 0.10). The inclusion/exclusion criteria have been carefully determined to take into account US standard of care for possible future US market considerations. If the study meets its primary over-all survival end-point, this could position AlloStim™ to potentially compete with ixabepilone (Ixempra™, made by Bristol-Myers Squibb) and Halaven™ (Eribulin Mesylate, made by Eisai), both which have recently received US FDA marketing approval for treatment of anthracycline, taxane and capecitabine resistant metastatic breast cancer.
Emmanuel Katsanis, MD, Chief Medical Officer and Chairman of the Scientific Advisory Board of ITL, stated: "Our Scientific Advisory Board, consisting of world-renowned experts in clinical cancer research and immunotherapy will be monitoring the scientific data generated from the clinical trial and will be advising on medical and scientific findings and data analysis. We believe the randomized trial design will provide us with information that will allow us to determine if AlloStim™ can extend the survival of women that have limited remaining treatment options for their metastatic disease."
Dr. Zivile Katiliene, Director of Regulatory Affairs and Clinical Operations at Immunovative Clinical Research, Inc. (wholly-owned subsidiary of ITL), stated: "We intend to conduct this Phase II/III trial under the Thailand regulatory guidelines and in accordance with the International Conference on Harmonization (ICH) requirements for Good Clinical Practice (GCP) international standards. The intent is to use the data from this trial to later support marketing applications in the USA and other jurisdictions, assuming the data reaches statistical significance in its primary over-all survival end-point. The use of foreign clinical data in support of a US marketing application is allowed under US regulations codified at 21 CFR 312.120. The US FDA has also issued a guidance to Industry explaining the requirements for FDA acceptance of foreign clinical data not conducted under a US IND. This guidance can be found by following this link: http://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM294729.pdf. In addition, this trial will have an independent Data Safety Monitoring Board (DSMB) that will be established in the USA to monitor the safety of the trial on a real-time basis. The radiology and pathology samples from all subjects will be read centrally by US licensed professionals affiliated with Immunovative Clinical Research, Inc. and immunological monitoring will be centralized and conducted by ITL in Jerusalem. ITL has developed standardized procedures for the collecting, processing, labeling, storage and shipment of blood, plasma and tumor samples in order to assure consistent and reliable data analysis. We will establish internal quality control and quality assurance protocols to ensure data integrity and frequent monitoring to ensure regulatory compliance."
Dr. Wirote Lausoontornsiri, principal investigator at the National Cancer Institute of Thailand, stated: "We have a long-standing collaboration with ITL. Our center conducted the first-in-human trials of AlloStim™ in 2009. This data was accepted by US FDA in support of ITL's Investigational New Drug (IND) application which was subsequently approved in August 2009 for conduct of the Phase I/II clinical trial in California. We have since conducted additional studies under a compassionate use exemption from 2010-2011 in Bangkok in order to optimize the treatment protocol and the logistics for formulating AlloStim™ in Jerusalem and shipping to Bangkok by cold-chain courier. These studies resulted in an improved protocol and validation of the shipping protocol ensuring the formulated living cell product maintained the pre-determined identity, function and stability requirements. Therefore, we feel we have the necessary experience to conduct this potentially pivotal Phase II/III clinical trial. We will be recruiting patients from all over Thailand to our modern facilities at NCI-Thailand in Bangkok. This will be the primary experimental trial available to our metastatic breast cancer patient population, therefore we believe we will be able to meet the accrual goals. We have experience conducting many types of clinical studies that are sponsored by the major pharmaceutical companies. Our data is regularly accepted by US FDA, EU, Japan, Korea and Taiwan as part of regulatory submissions. We consistently pass audits for compliance with GCP/ICH guidelines. It is our intent to carefully conduct this trial in order to document any potential harmful effects and to determine if the experimental drug has activity in this heavily pre-treated metastatic breast cancer population. We understand that ITL intends to use the data in support of future marketing applications and we will be allocating adequate staff and facilities to assure compliance with all regulations and will assure a scientifically valid outcome that will withstand international scrutiny."
Dr. Michael Har-Noy, CEO and founder of ITL, stated: "Metastatic breast cancer that is resistant to anthracycline, taxane and capecitabine remains a significant challenge. Current treatment options have little to no survival advantage and significant toxicity profiles. AlloStim™ represents a potential new class of treatment option for these women. We are pleased to have received Thai FDA approval to start the AlloStim™ Phase II/III clinical trial. This is a significant milestone for the Company, as it allows us to be able to prove in a controlled, randomized setting whether our drug candidate can provide heavily pre-treated metastatic breast cancer patients with a survival advantage. Our US IND remains on clinical hold, however we emphasize that we are not conducting this study in Thailand to avoid US FDA oversight. Rather, we determined that it would not be feasible to conduct a placebo-controlled study in this patient population in the United States. Therefore, we intended to conduct this study in Thailand even if the clinical hold were lifted. US patients have many off-label and experimental treatment options available and it was felt that these patients would not likely remain compliant with the trial requirement that restricts patients from obtaining additional therapy once accrued into the study. In Thailand, it is more likely that patients will comply as they do not have other treatment options once they have exhausted taxane, anthracycline and capecitabine, enabling us to conduct this study with a reasonable expectation for obtaining survival data without the complication of other treatments being added. We are discussing with US FDA the requirements to lift the clinical hold so we can conduct the recently announced investigator-sponsored studies planned to be conducted at Northwestern University and the University of Arizona. We intend to comply with any FDA requirements to lift the clinical hold and to assure the data from the Thailand clinical trial can be accepted by US FDA for a potential future licensing application."
Seth Shaw, CEO of IMUN, stated: "We are pleased that the compelling results from the AlloStim™ Phase I/II clinical trial has enabled ITL to convince regulatory authorities and the professionals at NCI-Thailand to advance this drug candidate to Phase II/III. Thai FDA approval represents a significant milestone in the development pathway toward commercialization of AlloStim™. This timely approval keeps us on schedule for launch of this potentially pivotal trial as planned in April 2013. Successfully meeting the stated primary end-point of statistically significant survival advantage is the next major value-added milestone target. Metastatic breast cancer represents a multi-billion dollar market. Our focus now will be on assuring adequate funding is available for this trial so that it can be executed flawlessly."
About Immunovative, Inc.:
On December 12th, 2011, Immunovative, Inc. ("IMUN") signed an exclusive License Agreement (the "License Agreement") with Immunovative Therapies, Ltd. ("ITL"). Under the terms of the License Agreement, IMUN has been granted an exclusive, worldwide license to commercialize any products covered under ITL's current issued and pending patent application portfolio, as well as the rights to any future patent applications, including improvements or modifications to the existing applications and any corresponding improvements or new versions of the existing products. Please visit IMUN's website at www.imun.com.
About Immunovative Therapies, Ltd.:
Immunovative Therapies, Ltd. is an Israeli biopharmaceutical company that was founded in May 2004 with financial support from the Israeli Office of the Chief Scientist. ITL is a graduate of the Misgav Venture Accelerator, a member of the world-renowned Israeli technological incubator program. The company was the Misgav Venture Accelerator's candidate for the prize for the outstanding incubator project of 2006, awarded by the Office of the Chief Scientist. ITL specializes in the development of novel immunotherapy drug products that incorporate living immune cells as the active ingredients for treatment of cancer and infectious disease. Please visit ITL's website at: www.immunovative.co.il
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For more information please contact:
Mr. Seth Shaw
Chairman & Chief Executive Officer
New York: +1-917-796-9926
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