On October 24, 2016 Inovio Pharmaceuticals, Inc. (NASDAQ:INO) reported that the U.S. Food and Drug Administration (FDA) has placed a clinical hold on its proposed phase III clinical program for VGX-3100 (Press release, Inovio, OCT 24, 2016, View Source [SID1234515974]). A clinical hold is a notification issued by the FDA to a trial sponsor to delay a proposed clinical trial or suspend an ongoing clinical trial. This study has not yet been initiated and has not enrolled or dosed subjects. Additionally, the hold does not pertain to any of Inovio’s other ongoing clinical studies.

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Inovio anticipates receiving a formal letter with complete information from the FDA within 30 days. In its initial communication, the FDA has requested additional data to support the shelf-life of the newly designed and manufactured disposable parts of the CELLECTRA 5PSP immunotherapy delivery device. Inovio is working diligently with the FDA to address its concerns and anticipates that the requested data will be available before the end of this year. Inovio estimates that the start of the phase III clinical program will be delayed until the first half of 2017 pending resolution of the FDA’s requests.

On October 24, 2016 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company committed to improving patient lives by manufacturing high quality products for biotechnology and pharmaceutical companies and advancing its proprietary R&D pipeline, reported the presentation of preclinical study data demonstrating that phosphatidylserine (PS)-targeting antibodies similar to bavituximab are able to enhance the anti-tumor activity of anti-PD-L1 therapy in a model of triple negative breast cancer (TNBC) (Press release, Peregrine Pharmaceuticals, OCT 24, 2016, View Source [SID1234515967]). Data showed that a combination of anti-PS and anti-PD-L1 therapies, with or without paclitaxel, led to greater anti-tumor responses than any of the treatments administered as single agents or dual treatment combinations with paclitaxel, in the well-characterized E0771 murine model of TNBC. Study results were presented by researchers from Duke University Medical Center at the American Association for Cancer Research (AACR) (Free AACR Whitepaper)’s Tumor Immunology and Immunotherapy Conference held October 20-23, 2016 in Boston, MA.

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In addition to evaluating the anti-tumor activity of the various treatment combinations, researchers also examined the impact of various traditional cancer therapies on PS expression in cancer cells. Study results confirmed that levels of PS expression were upregulated in E0771 and 4T1 TNBC cells following treatment with chemotherapy, radiation or photodynamic therapy. Photodynamic therapy also was shown to increase PS expression on tumor cells.

"These study results provide the latest support for the belief that PS-targeting therapies can enhance the anti-tumor activity of checkpoint inhibitors such as anti-PD-L1 therapy in the treatment of TNBC. Just last month, we announced results from another preclinical study in TNBC demonstrating that 80% of animals receiving the triple combination of anti-PS, anti-PD-1 and anti-LAG3 therapies experienced complete tumor regressions, whereas there were no animals in the anti-PD-1 and anti-LAG3 combination treatment arm that had a complete regression," said Jeff T. Hutchins, Ph.D., Peregrine’s vice president, preclinical research. "Additionally, these latest study findings related to increased PS expression on the surface of tumor cells following traditional cancer treatments demonstrate important activity within the tumor microenvironment that offers rationale for the potential of anti-PS agents in combatting cancer. We plan to continue to work with our collaborators at Duke University Medical Center to further study the therapeutic potential of PS-targeting agents in combination with checkpoint inhibitors like anti-PD-L1 and conventional therapies that augment immunotherapy mechanisms."

Bavituximab is an investigational monoclonal antibody that targets PS. Signals from PS inhibit the ability of immune cells to recognize and fight tumors. Bavituximab is believed to override PS mediated immunosuppressive signaling by blocking the engagement of PS with its receptors as well as by sending an alternate immune activating signal. Previous studies demonstrated PS-targeting antibodies shift the functions of immune cells in tumors, resulting in multiple signs of immune activation and anti-tumor responses. Peregrine evaluates the preclinical equivalent of bavituximab, ch1N11, in animal model studies to guide clinical development.

Peregrine’s clinical development strategy for bavituximab currently focuses on small, early-stage, proof-of-concept trials evaluating the drug in combination with other cancer treatments. This approach includes the recently announced grants by the National Comprehensive Cancer Network (NCCN) to support three different clinical trials of bavituximab treatment combinations. Those trials will evaluate novel bavituximab combinations in glioblastoma, head and neck cancer, and hepatocellular carcinoma including an immunotherapy combination. Additionally, Peregrine continues to advance its pre-clinical collaboration with Memorial Sloan Kettering Cancer Center with the goal of evaluating combinations of bavituximab with other checkpoint inhibitors and immune stimulatory agents. The intent behind this strategy is to focus our research and development spending to further validate bavituximab’s combination potential as we seek to advance the program though a pharmaceutical or biotechnology partner.

On October 24, 2016 Advaxis, Inc. (NASDAQ:ADXS), a clinical stage biotechnology company developing cancer immunotherapies, reported topline results from the early closure of stage 2 of the Phase 2 GOG-0265 trial, conducted by the Gynecologic Oncology Group (GOG, now part of NRG Oncology) and supported by the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI) (Press release, Advaxis, OCT 24, 2016, View Source [SID1234515966]).

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GOG-0265 is a single-arm, open-label Phase 2 multicenter study (NCT01266460) designed to evaluate the safety and activity of axalimogene filolisbac in patients with persistent or recurrent metastatic (squamous or non-squamous cell) carcinoma of the cervix (PRmCC) in a standard Simon two-stage design. The first stage of the study included a six-patient safety run-in and enrolled 26 patients. The first stage of the study was previously completed, meeting the predetermined safety and efficacy criteria required to proceed into the second stage of patient enrollment. The second stage enrolled 24 patients prior to the clinical hold that affected Advaxis’ clinical development programs last year. The second stage was not completed as designed due to the clinical hold.

A preliminary analysis of 12-month overall survival data from 24 patients enrolled in the second stage prior to the clinical hold showed that treatment with axalimogene filolisbac resulted in a 37.5 percent 12-month overall survival rate. These preliminary findings are consistent with earlier data that showed a 38.5 percent 12-month overall survival rate in 26 patients enrolled in the first stage of the study, despite modest differences in dosing schedules between the two stages.

Based on protocol defined prognostic factors of patients who enrolled in the study (n=50), a 12-month survival rate of 25 percent would have been expected. Comparing this 25 percent 12-month overall survival rate to the 38 percent 12-month overall survival rate actually observed across the total study population, treatment with axalimogene filolisbac resulted in a 52 percent increase in the expected 12-month overall survival rate.

"These data demonstrate a meaningful improvement in 12-month overall survival rate compared to historical GOG studies," said Warner K. Huh, M.D., division director of Gynecologic Oncology at the University of Alabama at Birmingham, and lead investigator of the study. "Historical survival rates for patients with PRmCC underscore the need for additional treatment options for patients and these results illustrate the promising therapeutic potential for axalimogene filolisbac in women with this rare cancer."

In the second stage of the study, 15 out of 24 patients experienced a Grade 1 or Grade 2 treatment-related adverse event (TRAE). The most common Grade 1 or Grade 2 TRAEs were hypotension and symptoms related to cytokine release (e.g., nausea, chills, fever). Nine out of 24 patients experienced a Grade 3 TRAE and two out of 24 patients experienced a Grade 4 TRAE, which were hypotension and symptoms related to cytokine release.

"We are very encouraged by these data and look forward to presenting and discussing a more detailed analysis of the trial results at an upcoming medical society meeting," said Daniel J. O’Connor, president and chief executive officer of Advaxis. "We believe that a more than 50 percent increase in 12-month overall survival rate is clinically meaningful, and Advaxis plans to pursue registrational opportunities in Europe in 2017."

Axalimogene filolisbac was recently classified as an advance therapy medicinal product (ATMP) in the EU, has received U.S. Food and Drug Administration (FDA) Fast Track Designation as an adjuvant therapy for treating high risk, locally advanced cervical cancer (HRLACC), and has been granted U.S. orphan drug designation for the treatment of invasive cervical cancer.

About Cervical Cancer

Cervical cancer is the fourth most common cancer in women worldwide.2 An estimated 13,000 new cases will be diagnosed in the United States in 2016, and 4,100 people will die of the disease, according to the National Cancer Institute. Persistent HPV infection is the most important factor in the development of cervical cancer, research shows.3,4 According to the ICO Information Centre on HPV and Cervical Cancer, about 4.4 percent of women in the United States are estimated to harbor high-risk cervical HPV infection at a given time, and about 72 percent of cervical cancers are attributed to high-risk HPV strains.5 The prognosis for women with advanced and recurrent cervical cancer remains poor, with survival of only 4 to 7 months following failure of first-line treatment, research has shown.6. According to the American Cancer Society, the 5-year mortality rate for metastatic disease is at just 17 percent, with the area continuing to be a high unmet medical need.7

About The GOG Foundation, Inc.

The GOG Foundation, Inc. (GOG), now part of NRG Oncology, is a non-profit international organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies. The GOG is committed to maintaining the highest standards in clinical trials development, execution, analysis and distribution of results. Continuous evaluation of its processes is utilized in order to constantly improve the quality of patient care. The GOG conducts clinical trials for patients with a variety of gynecologic malignancies, including cancers that arise from the ovaries, uterus, cervix, vagina and vulva. General information on many of these trials for medical professionals and the lay public can be obtained from ClinicalTrials.gov.

NRG Oncology is one of four adult US Network groups funded under the newly structured NCI National Clinical Trials Network. NRG Oncology is comprised of three legacy cooperative groups, the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG), and the Gynecologic Oncology Group (GOG).