On December 11, 2015 the U.S. Food and Drug Administration reported that it approved Alecensa (alectinib) to treat people with advanced (metastatic) ALK-positive non-small cell lung cancer (NSCLC) whose disease has worsened after, or who could not tolerate treatment with, another therapy called Xalkori (crizotinib) (Press release, , DEC 11, 2015, View Source [SID:1234508547]).
Lung cancer is the leading cause of cancer death in the United States, with an estimated 221,200 new diagnoses and 158,040 deaths in 2015, according to the National Cancer Institute. An ALK (anaplastic lymphoma kinase) gene mutation can occur in several different types of cancer cells, including lung cancer cells. ALK gene mutations are present in about 5 percent of patients with NSCLC. In metastatic cancer, the disease spreads to new parts of the body. In ALK-positive NSCLC metastatic patients, the brain is a common place for the disease to spread.

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"Today’s approval provides a new therapy for a group of patients who would have few treatment options once their disease no longer responds to treatment with Xalkori," said Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. "In addition to the primary effect on tumors in the lung, Alecensa clinical trials provide evidence of an effect on tumors that had spread to the brain, which is an important effect for clinicians to understand."

Alecensa is an oral medication that blocks the activity of the ALK protein, which may prevent NSCLC cells from growing and spreading.

The safety and efficacy of Alecensa were studied in two single-arm clinical trials of patients with metastatic ALK-positive NSCLC whose disease was no longer controlled by treatment with Xalkori. Study participants received Alecensa twice daily to measure the drug’s effect on their lung cancer tumors. In the first study, 38 percent of participants experienced a partial shrinkage of their NSCLC tumors, an effect that lasted for an average of 7.5 months. In the second study, 44 percent of participants experienced a partial shrinkage of their NSCLC tumors, lasting for an average of 11.2 months. The trials also examined Alecensa’s effect on individuals’ brain metastases, a common occurrence in this population. Sixty-one percent of participants in the two trials who had measurable brain metastases experienced a complete or partial reduction in their brain tumors, lasting an average of 9.1 months.

The most common side effects of Alecensa are fatigue, constipation, swelling (edema) and muscle pain (myalgia). Alecensa may cause serious side effects, including liver problems, severe or life-threatening inflammation of the lungs, very slow heartbeats and severe muscle problems. Treatment with Alecensa may cause sunburn when patients are exposed to sunlight.

Alecensa was approved using the accelerated approval regulatory pathway, which allows the FDA to approve products for serious or life-threatening diseases based on evidence that the product has an effect on an outcome that is reasonably likely to predict clinical benefit. In the case of Alecensa, the tumor response to treatment, along with the duration of response, provided this evidence. Under the accelerated approval requirements, a confirmatory study is required to verify and describe the clinical benefit of Alecensa.

The FDA granted the Alecensa application breakthrough therapy designation and priority review status. These are distinct programs intended to facilitate and expedite the development and review of certain new drugs in light of their potential to benefit patients with serious or life-threatening conditions. Alecensa also received orphan drug designation, which provides incentives such as tax credits, user fee waivers and eligibility for exclusivity to assist and encourage the development of drugs for rare diseases.

On December 10, 2015 ZIOPHARM Oncology, Inc. (Nasdaq:ZIOP), a biopharmaceutical company focused on new cancer immunotherapies, reported the presentation of the study design and a trial update for a Phase 1b/2 study of Ad-RTS-hIL-12 + veledimex following standard chemotherapy for the treatment of patients with locally advanced or metastatic breast cancer (Press release, Ziopharm, DEC 10, 2015, View Source [SID:1234508528]). The poster presentation, titled "Phase 1b/2 study of intratumoral Ad-RTS-hIL-12 + veledimex in patients with chemotherapy-responsive locally advanced or metastatic breast cancer," was presented as part of the "Ongoing Trials – Immunotherapy" session of the 2015 San Antonio Breast Cancer Symposium, and is available online at www.ziopharm.com.

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The study, which is being conducted at the Memorial Sloan Kettering Cancer Center in New York and began enrollment in June 2015, is designed to examine the safety, tolerability and efficacy of Ad-RTS-hIL-12 immunotherapy in up to 40 women with locally advanced or metastatic breast cancer of all subtypes. Ad-RTS-hIL-12 + veledimex is a novel gene therapy which controls local expression of IL-12 and may induce tumor stroma collapse and stimulation of an anti-cancer T cell immune response. The ability to regulate the production of IL-12 by modulating veledimex dosing is designed to improve its therapeutic index with standard of care.

Following entry into the trial, patients go on a chemotherapy holiday and enter an immunotherapy phase of treatment. A single cycle of Ad-RTS-hIL-12, along with the oral activator ligand veledimex, is given during the immunotherapy phase, with the goal of maintaining or improving pre-study response. Continuation of HER2-targeted antibody therapy is permitted during this immunotherapy phase for women with HER2+ disease. The study design allows for a review of the trial after every five subjects with HER2‑ and with HER2+ disease are treated. To date, five patients have been enrolled, including four with HER2- disease and one with HER2+ disease.

"Following standard of care treatment with an immunotherapy has the potential to deliver a one-two punch in breast cancer, particularly in a setting where IL-12, a potent immune cytokine, has demonstrated profound effects on the tumor environment," said Francois Lebel, M.D., Executive Vice President, Research and Development, Chief Medical Officer at ZIOPHARM. "We are pleased to see patient enrollment in this study accelerating and, beginning in 2016, look forward to understanding how the promise of this approach translates into outcomes."

On December 10, 2015 Navidea Biopharmaceuticals, Inc. (NYSE MKT: NAVB) treported that results from an investigator-initiated retrospective analysis demonstrated Lymphoseek (technetium Tc 99m tilmanocept) injection was successful in lymph node identification rate, node-positivity rate, and number of total nodes evaluated in sentinel lymph node biopsy (SLNB) procedures in clinically node-negative breast cancer patients undergoing neoadjuvant chemotherapy (NAT) compared to patients undergoing initial surgical treatment (Press release, Navidea Biopharmaceuticals, DEC 10, 2015, View Source;p=RssLanding&cat=news&id=2121860 [SID:1234508529]). These findings suggest that Lymphoseek offers breast surgeons the confidence to specifically identify and remove sentinel lymph nodes in this patient population. Results of the study conducted at the University of California, San Diego, School of Medicine, led by Anne Wallace M.D., professor of surgery, and Jonathan Unkart, M.D., Department of Surgery, UC San Diego Health, were presented today at the San Antonio Breast Cancer Conference in San Antonio, Texas.

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"Prior thinking suggests that neoadjuvant chemotherapy may induce fibrosis and inflammation that alters lymphatic drainage of axillary lymph nodes in breast cancer and may obscure lymphatic mapping procedures," said Dr. Wallace, who is also director of the Comprehensive Breast Health Center at UC San Diego Moores Cancer Center. "This analysis provides compelling evidence that Lymphoseek was successfully used for SLNB in the breast cancer neoadjuvant chemotherapy population and could potentially reduce the necessity for unnecessary and morbid axillary dissections, and improve the quality of life for patients.

"One of the most frequently asked questions we encounter from physicians is on the effectiveness of Lymphoseek in NAT patients," commented Michael Tomblyn, M.D., Navidea’s Chief Medical Officer. "These findings show Lymphoseek’s usefulness in the complicated NAT population and that the outcomes are not different from the standard breast cancer population."

The aim of the study was to compare identification rate, node-positivity rate and total number of nodes evaluated during SLNB with Lymphoseek and vital blue dye (VBD) in clinically node-negative patients receiving neoadjuvant endocrine or chemotherapy versus initial surgical treatment. A retrospective review of patients undergoing SLNB with Lymphoseek plus VBD from May 2013-2015 at UCSD was conducted. Of the 417 total sentinel lymph node (SLN) cases identified, 72 (17.2%) cases were in patients who had received NAT (61- chemo, 11- endocrine). The SLN identification rate was 100% in both groups (p=1.0). Overall, there were 68 (16.3%) cases of SLN-positivity, 14 (19.4%) in the NAT group versus 54 (15.7%) in the non-NAT group (p= 0.54). The median number of identified nodes was 3 in both groups. In the a zero-truncated negative binomial count model, age, surgeon and evaluating pathologist were significant predictors of the total number of SLNs evaluated. The use of NAT did not significantly affect the number SLNs evaluated.

About Lymphoseek

Lymphoseek (technetium Tc 99m tilmanocept) injection is the first and only FDA-approved receptor-targeted lymphatic mapping agent. It is a novel, receptor-targeted, small-molecule radiopharmaceutical used in the evaluation of lymphatic basins that may have cancer involvement in patients. Lymphoseek is designed for the precise identification of lymph nodes that drain from a primary tumor, which have the highest probability of harboring cancer. Lymphoseek is approved by the U.S. Food and Drug Administration (FDA), with or without scintigraphic imaging, for use in solid tumor cancers where lymphatic mapping is a component of surgical management and for guiding sentinel lymph node biopsy in patients with clinically node negative breast cancer, melanoma or squamous cell carcinoma of the oral cavity. Lymphoseek has also received European approval in imaging and intraoperative detection of sentinel lymph nodes in patients with melanoma, breast cancer or localized squamous cell carcinoma of the oral cavity.

Accurate diagnostic evaluation of cancer is critical, as it guides therapy decisions and determines patient prognosis and risk of recurrence. Overall in the U.S., solid tumor cancers may represent up to 1.2 million cases per year. The sentinel node label in the U.S. and Europe may address approximately 235,000 new cases of breast cancer, 76,000 new cases of melanoma and 45,000 new cases of head and neck/oral cancer in the U.S., and approximately 367,000 new cases of breast cancer, 83,000 new cases of melanoma and 55,000 new cases of head and neck/oral cancer diagnosed in Europe annually.

Lymphoseek Indication and Important Safety Information

Lymphoseek is a radioactive diagnostic agent indicated with or without scintigraphic imaging for:

Lymphatic mapping using a handheld gamma counter to locate lymph nodes draining a primary tumor site in patients with solid tumors for which this procedure is a component of intraoperative management.
Guiding sentinel lymph node biopsy using a handheld gamma counter in patients with clinically node negative squamous cell carcinoma of the oral cavity, breast cancer or melanoma.
Important Safety Information

In clinical trials with Lymphoseek, no serious hypersensitivity reactions were reported, however Lymphoseek may pose a risk of such reactions due to its chemical similarity to dextran. Serious hypersensitivity reactions have been associated with dextran and modified forms of dextran (such as iron dextran drugs).

Prior to the administration of Lymphoseek, patients should be asked about previous hypersensitivity reactions to drugs, in particular dextran and modified forms of dextran. Resuscitation equipment and trained personnel should be available at the time of Lymphoseek administration, and patients observed for signs or symptoms of hypersensitivity following injection.

Any radiation-emitting product may increase the risk for cancer. Adhere to dose recommendations and ensure safe handling to minimize the risk for excessive radiation exposure to patients or health care workers.

In clinical trials, no patients experienced serious adverse reactions and the most common adverse reactions were injection site irritation and/or pain (<1%).

On December 10, 2015 Biothera Pharmaceutical Inc., reported plans for a Phase 1b/2 clinical study in non-small lung cancer (NSCLC) patients to evaluate the ability of Biothera’s Imprime PGG to enhance responses to pembrolizumab (Keytruda), the anti-PD-1 antibody from Merck (NYSE:MRK), known as MSD outside the United States and Canada (Press release, Biothera Pharmaceuticals, DEC 10, 2015, View Source [SID1234562110]). Merck will provide funding and clinical supplies of pembrolizumab for the investigator-initiated study under the direction of Lawrence Feldman, M.D., of the University of Illinois at Chicago. The trial is expected to begin in the first quarter of 2016.

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Imprime PGG is a first-in-class, systemically administered beta glucan PAMP (pathogen associated molecular pattern) that triggers a robust, integrated immune response shown to enhance the anti-tumor efficacy of checkpoint inhibitors (PD-1, PD-L1 antibodies), anti-angiogenic antibodies and tumor-targeting monoclonal antibodies (mAbs). To date, Imprime PGG has shown promising efficacy in combination with mAbs in two Phase 2 studies of patients with NSCLC.

"Preclinical results for the combination therapy with Imprime PGG show the potential to expand the number of patients who can respond to Keytruda, as well as enhance the robustness of their response," said Dr. Feldman, Associate Professor of Medicine, College of Medicine at the University of Illinois at Chicago and principal investigator for the study. "The results for combination therapy with Imprime PGG have been encouraging, and I look forward to the progress of the upcoming study."

Biothera research has demonstrated that Imprime PGG activates key immune responses, including enhancement of dendritic cell maturation and presentation of antigen and co-stimulatory signals to T cells. The effect is to establish a critical link between the innate and adaptive immune systems, resulting in an expansion of T cell populations and inducing the production of the anti-tumor cytokine interferon gamma (IFN-γ). Imprime PGG also has been demonstrated to increase PD-L1 expression on tumor cells and tumor-associated macrophages, which also may enhance patient responses to pembrolizumab.

"Imprime PGG acts as an ignition switch to drive a coordinated response involving both the innate and adaptive immune systems to recognize and kill cancer cells," said Jose Iglesias, M.D., Chief Medical Officer, Biothera Pharmaceutical Inc. "In the anticipated Phase 1b/2 study, Imprime is expected to perform a dual role of enhancing antigen presentation, which helps more T cells target cancer, and upregulating PD-L1 expression to provide pembrolizumab more opportunities to disrupt or inhibit PD-1/PD-L1 interaction."

The Phase 1b/2 study is scheduled to begin dosing of patients in Q1 2016, with plans to enroll up to 58 patients with NSCLC following their progression on first line platinum-based chemotherapy. The phase 1b element of the trial is a dose-escalation study of up to 12 patients receiving Imprime PGG in combination with pembrolizumab. The phase 2 element of the study will test whether the addition of Imprime PGG to pembrolizumab increases median progression free survival and overall survival in up to 46 subjects.

On December 10, 2015 Peregrine Pharmaceuticals, Inc. (NASDAQ:PPHM) (NASDAQ:PPHMP), a biopharmaceutical company focused on developing therapeutics to stimulate the body’s immune system to fight cancer, reported financial results for the second quarter of fiscal year (FY) 2016 ended October 31, 2015, and provided an update on its advancing clinical pipeline and other corporate developments (Press release, Peregrine Pharmaceuticals, DEC 10, 2015, View Source [SID:1234508530]).

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Highlights Since July 31, 2015

"I am pleased to report that we are nearing completion of enrollment for our Phase III SUNRISE trial with over 90% of the intended number of patients enrolled. We have also made substantial progress toward initiating several new trials including a Phase II/III breast cancer study and a Phase II NSCLC trial in combination with AstraZeneca’s anti-PD-L1 antibody, durvalumab," said Steven W. King, president and chief executive officer of Peregrine. "Our goal is to transition our leading SUNRISE clinical sites into our new Phase II NSCLC trial which should significantly expedite study start-up activities. We are encouraged by the fact that a number of investigators from hospitals that participated in the SUNRISE trial have already enthusiastically agreed to participate in our upcoming NSCLC trial."

"As treatment paradigms shift to incorporate new drugs, it is clear that both chemotherapy and immuno-oncology agents will continue to be critical to patient care. Taken together, we believe our SUNRISE trial, as well as the newly planned breast and lung cancer trials will allow us to maximize the potential of bavituximab in both settings," said Joseph Shan, vice president of clinical and regulatory affairs of Peregrine. "We are committed to continuing to identify new potential indications, patient populations and therapies that can benefit from combination treatment with bavituximab. From what we have seen to date in our preclinical and translational studies, the opportunity appears vast, and we are hard at work converting the most promising prospects into true value."

Clinical Development Highlights

As of today, more than 90% of the planned number of patients have been enrolled in the Phase III SUNRISE trial, representing a sufficient number of patients required to trigger the two pre-planned interim analyses as well as the final analysis for trial unblinding. The company expects to reach the trial’s estimated enrollment of 582 patients in the coming weeks.

Peregrine and AstraZeneca expanded their cancer immunotherapy clinical trial collaboration to evaluate bavituximab in combination with AstraZeneca’s investigational anti-PD-L1 immune checkpoint inhibitor, durvalumab (MEDI4736). The companies are currently planning a global Phase II study in patients with previously treated squamous or non-squamous NSCLC, as well as a Phase I/Ib trial that will evaluate the safety and efficacy of bavituximab in combination with durvalumab and chemotherapy in multiple solid tumors. The company expects the Phase II study to be initiated in early 2016 with the Phase I/Ib study beginning later in 2016.

Peregrine continues to finalize plans for its Phase II/III trial to evaluate bavituximab with chemotherapy combinations in HER2-negative metastatic breast cancer. This trial is on track to be initiated by the end of calendar year 2015.

Supportive Research Highlights

Positive results were presented at the 2015 annual meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) from multiple new preclinical studies demonstrating enhanced anti-tumor activity and immune activation for combinations of a preclinical bavituximab equivalent and checkpoint inhibitors such as anti-PD-1 and anti-CTLA-4 in preclinical models of breast cancer and melanoma. Additionally, the company announced preliminary results for a new clinical test specifically designed to illustrate how bavituximab modulates immune responses in the tumor microenvironment.

New data presented at the International Association for the Study of Lung Cancer’s (IASLC’s) World Conference on Lung Cancer (WCLC) from a translational study of bavituximab demonstrated the ability of bavituximab, alone or in combination with docetaxel, to induce signs of immune activation in non-small cell lung cancer (NSCLC) patient-derived tumor samples, particularly when there was negative PD-L1 expression in the tumor sample. These data further support the potential mechanistic synergies for bavituximab with chemotherapy and checkpoint inhibitors targeting the PD-1/PD-L1 pathway.

Summary data presented at the Combination Immunotherapy Strategies session at the 10th Annual Immunotherapy and Vaccine Summit (ImVacS), highlighted key findings from several recent bavituximab-focused studies including: the potential of bavituximab to shift the tumor microenvironment from immuno-suppressive in which tumors evade immune detection to a state of immune activation in which the immune system recognizes and fights the tumor; bavituximab’s potential to increase the number of activated CD8+ cells in the tumor, which stimulates PD-1 expression, potentially increasing the number of patients able to respond to PD-1 and PD-L1 targeting immunotherapies; and, results from several clinical and preclinical studies in a range of tumor types showing that bavituximab and bavituximab-like antibodies, in combination with conventional therapy, have consistently demonstrated Kaplan-Meier graphs that follow the classic immunotherapy survival plateau.

Corporate Highlights

Peregrine closed a registered direct offering to a single institutional investor raising $20 million dollars. The funds raised from this financing will support the ongoing Phase III SUNRISE trial, and newly planned later-stage company-sponsored trials in breast cancer and NSCLC.

Avid Bioservices Highlights

"Our contract manufacturing business continues to strengthen with a 52% current quarter increase in revenue compared to the prior year period and year-to-date growth of 61%," stated Paul Lytle, chief financial officer of Peregrine. "Our new state-of-the-art manufacturing facility is now ready for the initial phase of GMP manufacturing and demand for Avid’s capacity continues to grow with our current backlog now at $49 million. Given the revenue growth and committed backlog, we are increasing our contract manufacturing revenue guidance to a range of $35 to $40 million for the full-year 2016."

During the second quarter of FY 2016, Avid Bioservices achieved record-breaking revenues generating approximately $9.5 million dollars, a 52% increase in revenue compared to the same quarter in the prior year.

Avid’s new manufacturing facility is now ready for the initial phase of GMP manufacturing. The state-of-the-art facility will accommodate single use bioreactors (SUBs) at up to 2,000 liter scale. Upcoming production runs will support late stage clinical development as well as process validation activities in anticipation of bavituximab and other client commercial product needs. The facility has the capacity to potentially generate approximately $40 million in new revenue annually.

Contract manufacturing committed backlog reached $49 million from existing customers covering services to be completed in FY 2016 and into FY 2017.

Financial Results

Total revenues for the second quarter of FY 2016 were $9,523,000, compared to $6,300,000 for the same quarter of the prior fiscal year. The increase was attributed to an increase in contract manufacturing revenue generated from Avid Bioservices.
Contract manufacturing revenue from Avid’s clinical and commercial biomanufacturing services provided to its third-party clients for the second quarter FY 2016 were $9,523,000, compared to $6,263,000 for the same quarter of the prior fiscal year. Peregrine expects third-party contract manufacturing revenue for the entire fiscal year to be between $35 million and $40 million, compared to previous guidance of $30 million to $35 million during last quarter’s earnings call. In addition to providing biomanufacturing services to its third-party clients, Avid will continue to support the clinical development and potential commercialization of bavituximab.

Total costs and expenses in the second quarter of FY 2016 were $23,347,000, compared to $18,437,000 in the second quarter of FY 2015. This increase was primarily attributable to current quarter increases in research and development expenses associated with the SUNRISE Phase III trial, newly planned later-stage company-sponsored trials in breast cancer and NSCLC, and an increase in the cost of contract manufacturing associated with higher reported revenue. For the second quarter of FY 2016, research and development expenses were $14,190,000, compared to $10,003,000 for the second quarter of FY 2015. For the second quarter of FY 2016, cost of contract manufacturing was $4,741,000, compared to $4,139,000 for the second quarter of FY 2015.
Peregrine’s consolidated net loss attributable to common stockholders was $14,578,000, or $0.07 per share, for the second quarter of FY 2016, compared to a net loss attributable to common stockholders of $13,131,000, or $0.07 per share, for the same prior year quarter.

Peregrine reported $72,005,000 in cash and cash equivalents as of October 31, 2015 compared to $68,001,000 at fiscal year ended April 30, 2015.

More detailed financial information and analysis may be found in Peregrine’s Quarterly Report on Form 10-Q, which will be filed with the Securities and Exchange Commission today.