1stOncology™: Cancer Intelligence Service – Page 15727 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

FDA Grants Special Protocol Assessment to Advaxis’ Phase 3 Study of AXAL in Patients with Cervical Cancer

On July 06, 2016 Advaxis, Inc. (NASDAQ:ADXS), a clinical stage biotechnology company developing cancer immunotherapies, reported that it reached an agreement with the U.S. Food and Drug Administration (FDA), under the Special Protocol Assessment (SPA) process, for the Phase 3 AIM2CERV trial evaluating the Company’s lead Lm immunotherapy candidate, axalimogene filolisbac (AXAL), in patients with high-risk, locally advanced cervical cancer (HRLACC) (Press release, Advaxis, JUL 6, 2016, http://ir.advaxis.com/press-releases/detail/1226/fda-grants-special-protocol-assessment-to-advaxis-phase-3-study-of-axal-in-patients-with-cervical-cancer [SID:1234513736]). AIM2CERV is a multinational, randomized, controlled clinical trial conducted in collaboration with The GOG Foundation, Inc. Trial enrollment will commence this summer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

A successfully concluded SPA provides a binding agreement with FDA’s review division that a pivotal trial design, conduct, and planned analysis adequately address the scientific and regulatory objectives in support of a regulatory submission for drug approval. Final marketing approval depends upon the efficacy results, safety profile and an evaluation of the risk/benefit of treatment demonstrated in the Phase 3 clinical trial.

In the 10-year period ending in 2013, only 25 percent of the requests for a SPA of oncology trials concluded with an FDA agreement.

"Receiving a SPA for the AIM2CERV trial is a testament to the promising AXAL results we have seen in cervical cancer patients," said Bradley Monk, M.D., Professor and Director of the Division of Gynecologic Oncology at Creighton University School of Medicine at St. Joseph’s Hospital and Medical Center and Lead Cervical Cancer Advisor to Advaxis. "The AIM2CERV trial will be a critical step in demonstrating that AXAL can be successful as an immunotherapy, with the trial’s goal to cure more women, and prevent disease recurrence."

"Collaborative discussions with the FDA led to a positive outcome with a SPA that clearly defines the clinical and regulatory pathway for the approval and commercialization of AXAL for the treatment of patients with HRLACC," said Daniel J. O’Connor, President and Chief Executive Officer. "Obtaining a SPA for the AIM2CERV Phase 3 protocol was our number one priority this year and it has now been achieved."

AXAL is a live attenuated Listeria monocytogenes bacteria bioengineered to target HPV-associated cancer. The primary objective of AIM2CERV is to compare the disease free survival of AXAL to placebo administered in the adjuvant setting following concurrent chemotherapy and radiotherapy (CCRT) administered with curative intent to patients with HRLACC. Secondary endpoints include examining overall survival and safety.

About Special Protocol Assessment

A SPA is an agreement with the FDA that the proposed trial protocol design, clinical endpoints and statistical analyses are acceptable to support the submission of an application for FDA’s determination of regulatory approval. For further information regarding the SPA process, please visit the FDA website, www.fda.gov.

About Cervical Cancer

Cervical cancer is the third most common malignancy in women worldwide. In the United States, nearly 13,000 new cases are diagnosed, and approximately 4,100 deaths are reported due to cervical cancer. According to the WHO/ICO Information Centre on HPV and Cervical Cancer, about 3.9 percent of women in the United States are estimated to harbor high-risk cervical HPV infection at a given time, and 71.7 percent of invasive cervical cancers are attributed to high-risk HPV strains.

About Axalimogene Filolisbac

Axalimogene filolisbac (AXAL) is Advaxis’ lead Lm Technology immunotherapy candidate for the treatment of patients with HPV-associated cancers and is in clinical trials for three potential indications: invasive cervical cancer, head and neck cancer, and anal cancer. In a completed randomized Phase 2 study in recurrent/refractory cervical cancer, AXAL showed apparent prolonged survival, objective tumor responses, and a manageable safety profile alone or in combination with chemotherapy, supporting further development of the Company’s Lm Technology. AXAL has Orphan Drug Designation in the U.S. for the treatment of anal cancer.

CEL-SCI REPORTS MONTHLY PATIENT ENROLLMENT IN JUNE FOR ITS PHASE 3 HEAD AND NECK CANCER TRIAL

On July 5, 2016 CEL-SCI Corporation (NYSE MKT: CVM) ("CEL SCI" or the "Company") reported that during the month of June it has enrolled 32 patients in its ongoing Phase 3 trial of its investigational immunotherapy Multikine* (Leukocyte Interleukin, Injection) in patients with advanced primary head and neck cancer (Press release, Cel-Sci, JUL 5, 2016, View Source [SID:1234513719]). Total patient enrollment for the trial is now 848 as of June 30, 2016.

About the Multikine Phase 3 Study

The Multikine Phase 3 study is enrolling patients with advanced primary (not yet treated) squamous cell carcinoma of the head and neck. The objective of the study is to demonstrate a statistically significant improvement in the overall survival of enrolled patients who are treated with the Multikine treatment regimen plus standard of care ("SOC") vs. subjects who are treated with SOC only.

About Multikine

Multikine is an investigational immunotherapeutic agent that is being tested in an open-label, randomized, controlled, global pivotal Phase 3 clinical trial as a potential first-line treatment for advanced primary squamous cell carcinoma of the head and neck. Multikine is designed to be a different type of therapy in the fight against cancer: one that appears to have the potential to work with the body’s natural immune system in the fight against tumors.

Multikine is also being tested in a Phase 1 study under a Cooperative Research and Development Agreement ("CRADA") with the U.S. Naval Medical Center, San Diego, and at University of California, San Francisco (UCSF), as a potential treatment for peri-anal warts in HIV/HPV co-infected men and women. Dr. Joel Palefsky, a world-renowned scientist and Key Opinion Leader (KOL) in human papilloma virus (HPV) research and the prevention of anal cancer, is the Principal Investigator at UCSF, which was added to the study in July 2015.

CEL-SCI has also entered into two additional co-development agreements for up to $3 million each with Ergomed Clinical Research Limited to further the development of Multikine for cervical dysplasia/neoplasia in women who are co-infected with HIV and HPV and for peri-anal warts in men and women who are co-infected with HIV and HPV.

PharmaCyte’s Research on Medical Uses of Cannabinoids Supported by Recent Scientific Article

On July 05, 2016 PharmaCyte Biotech, Inc. (OTCQB:PMCB), a clinical stage biotechnology company focused on developing targeted treatments for cancer and diabetes using its signature live-cell encapsulation technology, Cell-in-a-Box, reported that a recently published scientific article supports PharmaCyte’s ongoing research efforts that concern medical uses for constituents of Cannabis known as cannabinoids (Press release, PharmaCyte Biotech, JUL 5, 2016, View Source [SID:1234513713]). The article titled "Amyloid proteotoxicity initiates an inflammatory response blocked by cannabinoids" was published in the journal, Aging and Mechanisms of Disease and appeared online on June 23, 2016. The article can be viewed in its entirety at View Source

The Chief Executive Officer of PharmaCyte, Kenneth L. Waggoner, commented, "This research again demonstrates the potential benefit of cannabinoids in treating deadly and debilitating diseases such as cancer and neurodegenerative diseases. Our Cell-in-a-Box live-cell encapsulation technology provides a unique, versatile and natural platform for the delivery of potentially beneficial cannabinoids. It is PharmaCyte’s goal to use the combination of the Cell-in-a-Box technology and cannabinoids or cannabinoid-like compounds to develop effective and safe treatments for some of the deadliest forms of cancer for which such treatments do not presently exist, such as cancer of the pancreas, brain and breast, which affect hundreds of thousands of individuals worldwide every year."

The studies reported in the article, conducted by researchers at The Salk Institute for Biologic Studies and the University of California San Diego, showed that the inflammatory response initiated by "beta amyloid plaque" is blocked by cannabinoids. Beta amyloid plaque is an aggregating protein that has been linked to neurodegenerative conditions such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Accumulation of toxic beta amyloid plaque within nerve cells results in inflammation and nerve cell death. It is believed to be an early event in the development of many conditions associated with old age. The study showed that marijuana-derived cannabinoid molecules, such as tetrahydrocannabinol, stimulate the removal of beta amyloid plaque between neurons, block the inflammatory response and are thus protective against nerve cell death. This is the first study to show that cannabinoids affect both inflammation and amyloid beta accumulation in nerve cells. The implications are broad as there are currently no available drugs that significantly inhibit the cell death that is associated with these diseases.

Study Published in Nature Medicine Highlights Potential Role of FAK Inhibition in Pancreatic Cancer

On July 5, 2016 Verastem, Inc. (NASDAQ:VSTM), focused on discovering and developing drugs to treat cancer, reported the publication of preclinical research in the journal Nature Medicine by the Company’s researchers and scientific collaborators (Press release, Verastem, JUL 5, 2016, View Source;p=RssLanding&cat=news&id=2181887 [SID:1234513711]). The research, which was led by David G. DeNardo, PhD, Assistant Professor of Medicine, Division of Oncology, Department of Immunology, Washington University School of Medicine in St. Louis, and co-author of the paper, demonstrated that focal adhesion kinase (FAK) inhibition decreases fibrosis and immunosuppressive cell populations in pancreatic ductal adenocarcinoma (PDAC), rendering previously unresponsive tumors sensitive to chemo- and immunotherapy.

"The application of immunotherapy holds great promise to improve outcomes for patients with pancreatic cancer, as it has for melanoma and lung cancer patients," said Dr. DeNardo. "To date, however, attempts at immunotherapy in PDAC have achieved limited clinical benefit when deployed as single agents. This is likely due in part to the presence of a uniquely immunosuppressive tumor microenvironment which is dominant in most human cases of PDAC. Major drivers of this pro-tumorigenic microenvironment include a highly fibrotic stroma and extensive infiltration by immunosuppressive cell populations. Thus, agents that can potentially overcome excessive fibrosis while altering immune suppression would be particularly attractive targets for PDAC."

The paper, titled "Targeting Focal Adhesion Kinase Renders Pancreatic Cancers Responsive to Checkpoint Immunotherapy," (Jiang, et al., advanced online publication, July 4, 2016 (doi:10.1038/nm.4123) describes the therapeutic targeting of FAK in in vivo murine PDAC models. Prior research has demonstrated that hyperactivated FAK activity is a significant regulator of the fibrotic and immunosuppressive tumor microenvironment (TME) in PDAC tumor cells.

In this study, researchers show that FAK signaling is a key driver of fibrosis, immunosuppression and PDAC progression. It was then demonstrated that single-agent treatment with Verastem’s FAK inhibitor VS-4718 significantly limited tumor progression, resulting in a doubling of survival in an in vivo model of human PDAC. This slowing of tumor progression was associated with dramatically reduced tumor fibrosis, and a reduced number of tumor-infiltrating immunosuppressive cells. Given these findings, it was then hypothesized that the resulting effects of FAK inhibition on the TME may render PDAC tumors more sensitive to immunotherapy. Study results then demonstrated that FAK inhibition rendered previously unresponsive in vivo models responsive to T cell therapy and anti-PD1 antagonists. These data strongly support the ongoing clinical evaluation of FAK inhibitors in combination with checkpoint immunotherapy in patients with pancreatic cancer.

"FAK signaling has been shown to be important in several carcinomas, including pancreatic tumors, but its compelling role in creating an immunosuppressive tumor microenvironment is just emerging," said Jonathan Pachter, PhD, Chief Scientific Officer of Verastem, and co-author of the paper. "Another study, recently published in Cell, found that FAK inhibition can modulate certain immune cell populations, namely CD8+ T cells and Tregs, enabling an immune response that destroys tumors. Similarly, in the current study, we found that FAK inhibition alters tumor cell production of pro-inflammatory and immunosuppressive cytokines and reduces the tumor’s ability to avoid immune surveillance. Together these findings provide important support and rationale for the ongoing Phase 1 dose-escalation clinical study evaluating Verastem’s FAK inhibitor VS-6063 in combination with pembrolizumab and gemcitabine in patients with pancreatic cancer."

In early 2016, Verastem launched a new clinical development program focused on advancing its FAK inhibitors in combination with immuno-oncology agents and other current and emerging standard of care treatments. The Company’s lead FAK inhibitor, VS-6063 is currently being evaluated in a Phase 1 dose-escalation study at the Washington University in Saint Louis in combination with Merck & Co.’s PD-1 inhibitor pembrolizumab and gemcitabine in patients with pancreatic cancer. VS-6063 is also the subject of an additional clinical collaboration between Merck KGaA, Pfizer and Verastem where it will be evaluated in a Phase 1/1b study in combination with avelumab, an investigational fully human anti-PD-L1 IgG1 monoclonal antibody, in patients with advanced ovarian cancer. This collaboration trial is expected to begin during the second half of 2016.

About Focal Adhesion Kinase
Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase encoded by the PTK-2 gene that is involved in cellular adhesion and, in cancer, metastatic capability. VS-6063 (defactinib) and VS-4718 are orally available compounds that are potent inhibitors of FAK. VS-6063 and VS-4718 utilize a multi-faceted approach to treat cancer by reducing cancer stem cells, enhancing anti-tumor immunity, and modulating the local tumor microenvironment. VS-6063 and VS-4718 are currently being studied in multiple clinical trials for patients with cancer.

Five Prime Therapeutics Receives FDA Orphan Drug Designation for FPA144 for the Treatment of Gastric Cancer

On July 05, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation to FPA144 for the treatment of gastric cancer, including cancer of the gastroesophageal junction in patients whose tumors overexpress FGFR2b (Press release, Five Prime Therapeutics, JUL 5, 2016, View Source [SID:1234513712]). FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy.

"Patients with advanced gastric cancer whose tumors overexpress FGFR2b have a significant unmet medical need, and the literature suggests that they have an especially poor prognosis," said Robert Sikorski, M.D., Ph.D., senior vice president and chief medical officer. "The initial single-agent efficacy and safety data seen so far during the ongoing FPA144 Phase 1 study is encouraging, and we look forward to further exploring FPA144 as a potential treatment for patients with gastric cancer."

Orphan Drug Designation is granted by the FDA Office of Orphan Drug Products to products that treat rare diseases. The FDA defines rare diseases as those affecting fewer than 200,000 people in the United States. Orphan Drug Designation provides the sponsor certain benefits and incentives, including a period of marketing exclusivity if regulatory approval is received for the designated indication, as well as potential tax credits and waiver of certain administrative fees.

About Gastric Cancer
Globally, gastric cancer is the sixth most common malignancy with the third highest mortality. The prevalence of gastric cancer worldwide is approximately 1.5 million patients, of which an estimated 5%, or approximately 80,000 patients, have FGFR2 gene-amplified tumors that overexpress FGFR2b. There are an estimated 76,000 gastric cancer patients in the United States, but the prevalence of gastric cancer is much higher in Asia and other regions of the world.

About FPA144
FPA144 is an anti-FGF receptor 2b (FGFR2b) humanized monoclonal antibody in clinical development as a targeted immune therapy for tumors that over-express FGFR2b, as determined by a proprietary immunohistochemistry (IHC) diagnostic assay. FGFR2 gene amplification (as identified by FISH) is found in a number of tumors, including in approximately 5% of gastric cancer patients, and is associated with poor prognosis.

FPA144 is designed to block tumor growth through two distinct mechanisms. First, it has been engineered to drive immune-based killing of tumor cells by antibody-dependent cell-mediated cytotoxicity (ADCC) and the recruitment of natural killer (NK) cells and T cells. Second, it binds specifically to FGFR2b and prevents the binding of certain fibroblast growth factors that promote tumor growth. When combined with PD-1 blockade, FPA144 has shown an additive effect in tumor growth inhibition in preclinical models. Five Prime retains global development and commercialization rights to FPA144.