On January 17, 2017 Xcovery, a developer of targeted therapeutics for cancer, reported their participation in the NCI Formulary, a public-private partnership between the National Cancer Institute (NCI), part of the National Institutes of Health (NIH), and pharmaceutical and biotechnology companies to expedite the use of agents in clinical trials (Press release, Xcovery, JAN 17, 2017, View Source [SID1234517433]). The partnership, which launched last week with fifteen targeted agents from six pharmaceutical companies, will seek to alleviate the lengthy process to develop new therapies for patients, and respond to the call for greater collaboration within the industry made by Vice President Biden’s Cancer Moonshot Initiative.

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"Collaboration among pharmaceutical companies with the NCI and the NIH will speed up the development of novel therapies and benefits for patients down the line," said Lieming Ding, M.D., Chairman of Xcovery. "Xcovery has focused on developing drugs with reduced toxicity, which allows for combination therapies. We’re excited to join the NCI Formulary by providing our ALK inhibitor, ensartinib, to the broad research community for additional development opportunities, particularly in combination therapy programs."

Research indicates that combination therapies, which include drugs with different mechanisms of action impacting cancer cells in multiple ways, provide an improved clinical benefit and can decrease the risk of relapse. The establishment of the NCI Formulary will enable the NCI to facilitate and streamline the arrangements for access to and use of pharmaceutical agents from multiple organizations, allowing for further research on various therapeutic opportunities. Following Xcovery’s approval, investigators will be able to obtain and test ensartinib in new preclinical or clinical studies, including combination studies with formulary agents from different companies.

About Ensartinib

Ensartinib (X-396) is a potent anaplastic lymphoma kinase (ALK) inhibitor currently in a global Phase 3 trial in ALK positive non-small cell lung cancer (NSCLC) patients. Besides ALK, ensartinib also potently inhibits TRKA fusions, TRKC, ROS1, EphA2, and c-MET.

On January 17, 2017 The German National Center for Tumor Diseases (NCT) Heidelberg and Protagen AG reported a collaboration to utilize Protagen’s SeroTag technology to identify biomarkers that predict therapy responsiveness and the detection of immune-related adverse events (irAEs) in melanoma patients treated with checkpoint inhibitors (Press release, Protagen, JAN 17, 2017, View Source [SID1234517430]).

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Checkpoint inhibitors offer great potential for the treatment of many indications, including melanoma. Yet, only a subset of patients respond favorably to such treatment and it is not currently possible to predict who will benefit from the therapy in clinical routine. In addition, checkpoint inhibitors also trigger immune-related Adverse Events (irAEs) and even the onset of autoimmune diseases. Through this collaboration, Protagen and NCT will utilize Protagen‘s proprietary immune system profiling platform to predict response, monitor patients and detect immune related adverse events.

PD Dr. Jessica Hassel from the DermatoOncologic department of the Department of Dermatology and the NCT commented: "Checkpoint inhibitors offer exciting potential to cure cancer patients. However, at least half of the patients with a metastasized melanoma do not benefit long-term. Response rates can be increased via combination therapies such as a combination of ipilimumab and nivolumab, but such combinations also significantly increase the risk of suffering from sometimes serious irAEs, which have prevalence as high as 60% in these patients. To overcome the challenges posed by irAEs and to better select the appropriate therapy for each patient, we must learn more about the immune system status of these patients in general and their production of specific autoantibodies. Utilizing Protagen’s SeroTag platform enables this insight and we look forward to this collaboration."

Dr. Peter Schulz-Knappe, Protagen’s Chief Scientific Officer, added: "Our unique SeroTag technology has already proven that it can be used to define homogeneous patient subgroups in autoimmune diseases with the potential to predict treatment response. Based on the link between immuno-oncology and autoimmune disease, it is a natural extension to apply our profiling approach to checkpoint inhibitors to address some of the most challenging questions in this field. We feel privileged that Dr. Hassel and the NCT share this view and we are excited about our collaboration."

On January 17, 2017 Agenus Inc. (NASDAQ: AGEN), an immuno-oncology company with a pipeline of immune checkpoint antibodies and cancer vaccines, reported a clinical trial collaboration with the National Cancer Institute (NCI) (Press release, Agenus, JAN 17, 2017, View Source [SID1234517428]). The double-blind, randomized controlled Phase 2 trial will evaluate the effect of Agenus’ personalized autologous vaccine candidate, Prophage (HSPPC-96), in conjunction with Merck’s pembrolizumab on the overall survival rate of patients with newly diagnosed glioblastoma (ndGBM). The trial will be conducted by the Brain Tumor Trials Collaborative (BTTC), a consortium of top academic centers led by Dr. Mark Gilbert, Chief of the Neuro-Oncology Branch at the NCI Center for Cancer Research.

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The trial aims to assess the efficacy of PD-1 targeted checkpoint blockade in combination with a heat-shock protein based vaccine candidate in an indication in which this vaccine has shown improved progression-free survival, as presented at ASCO (Free ASCO Whitepaper) 2015. It is a two-arm trial with one arm receiving pembrolizumab as a monotherapy and a second arm receiving both Prophage and pembrolizumab in combination. Forty-five patients will be randomly assigned to each arm.

Under this collaboration, Agenus will supply Prophage, Merck will provide pembrolizumab (Keytruda) and NCI and BTTC member sites will recruit patients and conduct the trial.

About Prophage
Prophage is an individualized autologous vaccine candidate derived from proteins extracted from the patient’s tumor. The vaccine candidate consists of heat shock protein peptide complexes that include the chaperone gp-96 (HSPPC-96) naturally bound to tumor protein fragments. Administration of HSPPC-96 bearing the precise antigenic fingerprint of the patient’s particular cancer represents an effective immune education strategy that enhances recognition of a tumor as ‘non-self’ leading to a potent anti-tumor immune response.

In a Phase 2 study of Prophage monotherapy, patients with ndGBM exhibited an improved progression-free and overall survival as compared to historical control with standard of care.

About KEYTRUDA (pembrolizumab)
KEYTRUDA is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells. KEYTRUDA is indicated for the treatment of patients with unresectable or metastatic melanoma; for the first-line treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (TPS ≥50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations and upon disease progression on or after platinum-containing chemotherapy in patients with NSCLC whose tumors express PD- L1 (TPS ≥1); and for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. KEYTRUDA is administered as an intravenous infusion every three weeks for the approved indications.

For Safety and Prescribing Information for KEYTRUDA (pembrolizumab), please see View Source

On January 17, 2017 TESARO, Inc. (NASDAQ:TSRO), an oncology-focused biopharmaceutical company, reported the opening of an expanded access program (EAP) in the United States for the investigational PARP inhibitor, niraparib (Press release, TESARO, JAN 17, 2017, View Source [SID1234517426]). Through this program, niraparib is being made available for eligible women with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer following a complete or partial response to platinum-based chemotherapy. Healthcare professionals can learn more about the niraparib EAP by visiting www.niraparibEAP.com. An EAP for niraparib in Europe is planned to open in the first half of 2017, and will be initiated on a country-by-country basis.

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Expanded access programs enable patients with serious or life-threatening illnesses who do not otherwise qualify for participation in a clinical trial, and for whom there are no comparable or satisfactory alternate therapies, to access investigational medicines.

"Ovarian cancer is the fifth most frequent cause of cancer death among women in the United States, yet there have been few advances in the treatment of ovarian cancer in over a decade," said Mary Lynne Hedley, Ph.D., President and COO of TESARO. "The niraparib EAP will provide a mechanism by which eligible women with ovarian cancer may benefit from access to this investigational therapy, which has been accepted for priority review by the U.S. FDA."

About the Niraparib Expanded Access Program
The niraparib EAP is a program for women with recurrent, ovarian, fallopian tube, or primary peritoneal cancer following a complete or partial response to platinum. This EAP is being administered on behalf of TESARO by the Idis Managed Access division of Clinigen Group plc. U.S. based healthcare professionals seeking more information about the niraparib EAP can call Idis Managed Access at 1-877-768-4303 or email [email protected] for further details. Patients who are interested in enrolling in the niraparib EAP should speak with their physician to understand if niraparib is an appropriate option. Niraparib is an investigational agent and, as such, has not been approved by the U.S. Food and Drug Administration (FDA) or any other regulatory agencies in any markets. Additional information about the niraparib EAP, including a list of Frequently Asked Questions, is available at www.niraparibEAP.com.

An EAP for niraparib in Europe is planned to open in the first half of 2017, and will be initiated on a country-by-country basis.

About Niraparib
Niraparib is an oral, once-daily PARP inhibitor that is currently being evaluated in three pivotal trials. TESARO is building a robust niraparib franchise by assessing activity across multiple tumor types and by evaluating several potential combinations of niraparib with other therapeutics. The ongoing development program for niraparib includes a Phase 3 trial in patients who have received first-line treatment for ovarian cancer (the PRIMA trial), a registrational Phase 2 trial in patients who have received multiple lines of treatment for ovarian cancer (the QUADRA trial), and a Phase 3 trial for the treatment of patients with germline BRCA-mutated, metastatic breast cancer (the BRAVO trial). Several combination studies are also underway, including trials of niraparib plus pembrolizumab and niraparib plus bevacizumab. Janssen Biotech has licensed rights to develop and commercialize niraparib specifically for patients with prostate cancer worldwide, except in Japan.

The niraparib New Drug Application (NDA) has been accepted for priority review by the FDA and is supported by data from the ENGOT-OV16/NOVA trial, a double-blind, placebo-controlled, international Phase 3 study that enrolled 553 patients with recurrent ovarian cancer following complete or partial response to their most recent platinum-based chemotherapy. The full results of the ENGOT-OV16/NOVA trial were presented in detail at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) 2016 Congress in Copenhagen on October 8, 2016 by Dr. Mansoor Raza Mirza, M.D., Medical Director of the Nordic Society of Gynecologic Oncology (NSGO) and principal investigator. These data were simultaneously published in the New England Journal of Medicine.

Niraparib is an investigational agent and, as such, has not been approved by the U.S. FDA, European Medicines Agency (EMA), or any other regulatory agencies.

About Ovarian Cancer
Approximately 22,000 women are diagnosed each year with ovarian cancer in the United States, and more than 65,000 women are diagnosed annually in Europe. Ovarian cancer is the fifth most frequent cause of cancer death among women. Despite high response rates to platinum-based chemotherapy in the second-line advanced treatment setting, approximately 85% of patients will experience recurrence within two years. If approved, niraparib may address the difficult "watchful waiting" periods experienced by patients with recurrent ovarian cancer in between cycles of platinum-based chemotherapy.

On January 17, 2017 Celsion Corporation (NASDAQ:CLSN) reported data from the fourth cohort of patients in its Phase Ib dose escalating clinical trial (the OVATION Study) combining GEN-1, the Company’s IL-12 gene-mediated immunotherapy, with the standard of care for the treatment of newly-diagnosed patients with Stage III and IV ovarian cancer who will undergo neoadjuvant chemotherapy followed by interval debulking surgery (Press release, Celsion, JAN 17, 2017, View Source [SID1234517425]). In the first twelve patients dosed in the OVATION Study, GEN-1 plus standard chemotherapy produced impressive results, with no dose limiting toxicities and highly promising efficacy signals in this difficult to treat cancer.

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"These early results have impressed our investigators which accounts for the rapid patient accrual in the study. The consistency and robust nature of the data across all four cohorts and the encouraging clinical responses underscore the potential of GEN-1 to serve as an effective, safe IL-12 immunotherapy in ovarian cancer," said Nicholas Borys, M.D., Celsion’s chief medical officer. "In particular, we see improvements across a number of important and meaningful measures used to assess ovarian cancer, which reinforce our confidence in this IL-12 immunotherapy approach and provide a strong rationale for continued development of GEN-1 for the treatment of ovarian cancer. We look forward to the translational data which, along with the clinical findings, will assist in the design of our registrational program."
The OVATION Study is designed to enroll three to six patients per dose cohort with the goal of identifying a safe, tolerable and immunologically active dose of GEN-1 by recruiting and maximizing an immune response. The first four cohorts have each enrolled three patients. Enrollment in the fourth cohort is ongoing with the goal of enrolling three additional patients in this final dose cohort. Celsion expects to complete enrollment in the OVATION Study this quarter and report final data, including translational data for all patients in the second quarter of 2017. Future studies of GEN-1 will include a Phase I/II study combining GEN-1 with Avastin and Doxil.

OVATION Study – Totality of Results in the First Four Patient Cohorts
Of the first twelve patients dosed, one patient demonstrated a complete response (CR), eight patients demonstrated a partial response (PR) and three patients demonstrated stable disease (SD), as measured by RECIST criteria. This translates to a 100% disease control rate (DCR), and 75% objective response rate (ORR). These results compare very favorably to the current standard of care.

Eleven patients had successful resections of their tumors, with six patients having an optimal R0 resection, which indicates a microscopically margin-negative resection in which no gross or microscopic tumor remains in the tumor bed, and four patients with a R1 resection, indicating microscopic residual tumor. One patient had an R2, indicating macroscopic residual tumor. One patient in the second cohort was ineligible for debulking surgery due to a medical complication unrelated to the study or the study drug.

Of the eleven surgically treated and evaluable patients, one patient demonstrated a complete pathological response (cPR), five patients demonstrated a micro pathological response (microPR), and five patients demonstrated a macroPR. These data compare favorably to historical data, which indicate that cPRs are typically seen in less than 7% of patients receiving neoadjuvant chemotherapy followed by surgical resection. cPRs have been associated with a median overall survival of 72 months, which is more than three years longer than those who do not experience a cPR. In addition, microPRs are seen in approximately 30% of patients, and are associated with a median overall survival of 38 months&supl;.

All eleven patients who completed treatment follow-up experienced a dramatic (greater than 90%) drop in their CA-125 protein levels as of their most recent study visit. CA-125 is used to monitor certain cancers during and after treatment. CA-125 is present in greater concentrations in ovarian cancer cells than in other cells. A 50% reduction in CA-125 levels is considered meaningful.

OVATION Study – Top Line Translational Data from First Two Cohorts
Celsion previously reported initial translational data from the first two cohorts of the OVATION study. Tumor and blood samples collected before the start of the neoadjuvant chemotherapy (NACT) and after the completion of GEN-1 treatment at debulking surgery are being analyzed for immune cell populations. Top line data demonstrates intriguing immunological changes in the tumor that are consistent with the activation of the immune system. For example, the ratio of CD8+/FoxP3+ cells was increased in all four evaluable patients. High tumor infiltrating CD8+ T-cell density, low FoxP3+ T-cell density or high CD8+/FoxP3+ ratio demonstrate a potential shift in tumor environment to favoring immune stimulation following NACT + GEN-1 therapy. For the remaining two patients the post-treatment tumor tissue was not available. In one of those two patients there was complete pathological response hence no tumor tissue was present to provide a post-treatment comparison. In the other patient the debulking surgery was not performed due to disease related complications. Complete immune analysis of biological tissue including cytokine ELISA from all four patient cohorts is in progress.

"These results build on the impressive clinical findings we observed in our earlier GOG Study as well as the translational data from this same study. As we move closer towards the final design of a Phase I/II trial to evaluate the synergistic anti-cancer effects of GEN-1 together with Avastin and Doxil, these results also provide strong clinical evidence for the potential of GEN-1 in ovarian cancer," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "We anticipate completion of enrollment in the fourth and final patient cohort in the coming quarter. In parallel, we are currently collecting full translational data from the study, which we expect to report in the first half of this year."