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Tesaro Announces Opening of Niraparib Expanded Access Program for U.S. Patients With Ovarian Cancer

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.

Celsion Announces Continuing Positive Data from the OVATION Study in Newly Diagnosed Advanced Ovarian Cancer Patients

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.

"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."

Kura Oncology Doses First Patient in Phase 2 Study of Tipifarnib in Chronic Myelomonocytic Leukemia

On January 17, 2017 Kura Oncology, Inc. (Nasdaq:KURA), a clinical stage biopharmaceutical company, reported that the first patient has been dosed in its Phase 2 clinical trial of tipifarnib in patients with chronic myelomonocytic leukemia (CMML) (Press release, Kura Oncology, JAN 17, 2017, View Source [SID1234517423]).

"Objective responses, including complete responses, have been previously observed with tipifarnib in CMML. Our goals with this Phase 2 study are to confirm the level of activity of tipifarnib in this patient population as well as to validate biomarker hypotheses that may allow us to identify those patients most likely to experience durable responses," said Antonio Gualberto, M.D., Ph.D., Chief Medical Officer of Kura Oncology.

"New pharmaceutical treatments are urgently needed to combat this rare disease," said Eric Padron, M.D., of the Department of Hematologic Malignancies at H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida, a clinical investigator on this study. "Given the previous results obtained with tipifarnib in this setting and the potential to identify genetic biomarkers to prospectively select patients in future studies, we are excited to evaluate tipifarnib as a potential therapeutic for CMML."

This Phase 2 clinical trial is designed to enroll approximately 20 patients with CMML and will evaluate the antitumor activity of tipifarnib in terms of overall response rate. Patients will receive tipifarnib administered orally, twice a day for 7 days in alternating weeks in 28 day cycles. Patient samples will be analyzed for the presence or absence of various biomarkers potentially relevant to the activity of tipifarnib. Additional information about this clinical trial is available at clinicaltrials.gov using the identifier: NCT02807272.

About Chronic Myelomonocytic Leukemia

CMML is a clonal disorder of bone marrow stem cells that shares characteristics of both myeloproliferative and myelodysplastic diseases. CMML is characterized by increased monocytes and blasts in the peripheral blood and bone marrow, as well as dysplasia in at least one type of blood cell. CMML is estimated to have an annual incidence of approximately 1,400 patients in the United States. These patients generally have a poor prognosis due to limited therapeutic options with only a 29% survival rate three years after diagnosis.

About Tipifarnib

Kura Oncology’s lead program, tipifarnib, is an inhibitor of farnesylation, a key cell signaling process implicated in cancer initiation and development. In extensive clinical trials, tipifarnib has shown a well-established safety profile and compelling and durable anti-cancer activity in certain patient subsets. Preclinical and clinical data suggest that, in the appropriate context, tipifarnib has the potential to provide significant benefit to cancer patients with limited treatment options. Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics and tumor biology, Kura Oncology is seeking to identify patients most likely to benefit from tipifarnib.

BioLineRx Announces Initiation of Immuno-Oncology Phase 2 Study to Investigate Combination of BL-8040 and KEYTRUDA® for Pancreatic Cancer

On January 17, 2017 BioLineRx Ltd. (NASDAQ/TASE: BLRX), a clinical-stage biopharmaceutical company dedicated to identifying, in-licensing and developing promising therapeutic candidates, reported the initiation of a second Phase 2a trial investigating BL-8040 in combination with KEYTRUDA (pembrolizumab), MSD’s anti-PD-1 therapy, in patients with metastatic pancreatic cancer (Filing, 6-K, BioLineRx, JAN 17, 2017, View Source [SID1234517419]). The study is part of a research collaboration between MSD and MD Anderson Cancer Center.

The open-label, single center, single-arm Phase 2a study aims to evaluate the potential of BL-8040 in combination with KEYTRUDA in pancreatic cancer and focuses on the mechanism-of-action by which both drugs might synergize. In addition to assessing clinical response, the study includes multiple assessments to evaluate the biological anti-tumor effects induced by the combination.

In August 2016, the Company announced the signing of a collaboration agreement with The University of Texas MD Anderson Cancer Center for the investigation of BL-8040 in combination with KEYTRUDA in pancreatic cancer. The investigator-sponsored study is part of a strategic, immuno-oncology, clinical research collaboration between MSD (known as Merck in the US and Canada) and MD Anderson Cancer Center aimed at evaluating Merck’s anti-PD-1 therapy, KEYTRUDA, in combination with various treatments and novel drugs.

Philip Serlin, Chief Executive Officer of BioLineRx, said, "This is the second Phase 2 immuno-oncology trial taking place to investigate the combination of BL-8040 and KEYTRUDA for the treatment of pancreatic cancer. In September 2016, we announced the initiation of the COMBAT study, our first Phase 2a study for evaluating the clinical efficacy of BL-8040 in combination with KEYTRUDA, also for the treatment of patients with pancreatic cancer. The COMBAT study, which is being conducted by BioLineRx under a collaboration agreement between BioLineRx and MSD is also currently recruiting patients. We believe that the trial announced today will support the COMBAT study and deepen our understanding of the mechanism-of-action of the combination treatment."

"We also believe that the combination of BL-8040 with KEYTRUDA has the potential to expand the benefit of immunotherapy to non-respondent patients and cancer types currently resistant to immuno-oncology treatments, such as pancreatic cancer. Furthermore, BL-8040’s inhibition of CXCR4, which may affect the immunosuppressive tumor micro-environment, is potentially synergistic with immune checkpoint inhibitors in additional oncological indications," added Mr. Serlin.

Dr. David Fogelman, from MD Anderson Cancer Center, the principal investigator of the trial, stated, "We hope that BL-8040 will prime the immune system and increase the anti-tumor activity of Keytruda. We have designed the study to look for evidence of this, both in the tumors themselves and in the patient as a whole. If this combination is successful, we will move pancreatic cancer research forward in a new direction."

BL-8040, BioLineRx’s lead oncology platform, is a CXCR4 antagonist that has been shown in several clinical trials to be a robust mobilizer of immune cells and to be effective at inducing direct tumor cell death. Additional findings in the field of immuno-oncology suggest that CXCR4 antagonists may be effective in inducing the infiltration of anti-tumor T cells into the tumor. Therefore, when combined with KEYTRUDA, which blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, BL-8040 has the potential to enable activated T cells to better reach tumor cells in the fight against pancreatic cancer.

About Pancreatic Cancer
Pancreatic cancers of all types are the seventh most common cause of cancer deaths. According to the American Cancer Society, in 2015, nearly 50,000 were diagnosed with pancreatic cancer and an estimated 40,000 will die from the disease. The most common type of pancreatic cancer is pancreatic adenocarcinoma, which accounts for about 85 percent of cases. These adenocarcinomas start within the part of the pancreas that makes digestive enzymes. There are usually no symptoms in the early stages of the disease and symptoms that are specific enough to suggest the onset of pancreatic cancer typically do not develop until the disease has reached an advanced stage. The five-year survival rate of pancreatic adenocarcinoma is around seven percent.

About BL-8040
BL-8040 is a short peptide for the treatment of acute myeloid leukemia, solid tumors, and certain hematological indications. It functions as a high-affinity antagonist for CXCR4, a chemokine receptor that is directly involved in tumor progression, angiogenesis, metastasis and cell survival. CXCR4 is over-expressed in more than 70% of human cancers and its expression often correlates with disease severity. In a number of clinical and pre-clinical studies, BL-8040 has shown robust mobilization of cancer cells from the bone marrow, thereby sensitizing these cells to chemo- and bio-based anti-cancer therapy, as well as a direct anti-cancer effect by inducing apoptosis. In addition, BL-8040 has also demonstrated robust stem-cell mobilization, including the mobilization of colony-forming cells, and T, B and NK cells. BL-8040 was licensed by BioLineRx from Biokine Therapeutics and was previously developed under the name BKT-140.

AstraZeneca expands 1st-line lung cancer Immuno-Oncology programme opportunities

On January 17, 2017 AstraZeneca reported an update on its Immuno-Oncology (IO) late-stage clinical development programme in 1st-line non-small cell lung cancer (NSCLC), including a refinement of the Phase III MYSTIC trial (Press release, AstraZeneca, JAN 17, 2017, View Source [SID1234517418]).

The MYSTIC trial was initially designed to assess the benefit of durvalumab monotherapy and durvalumab and tremelimumab (durva + treme) combination therapy versus standard-of-care (SoC) chemotherapy, focused on progression-free survival (PFS).

The MYSTIC trial will now assess PFS and overall survival (OS) endpoints in patients with PDL1-expressing tumours for both durvalumab monotherapy and the combination of durva + treme, as well as in ‘all comers’ for the combination of durva + treme, versus SoC chemotherapy.

While the focus remains on exploring the benefit of durva + treme as combination therapy, the Company has updated the endpoints of the MYSTIC trial to include OS and PFS in durvalumab monotherapy. This is based on recent internal and external data, including durvalumab’s strong efficacy in monotherapy presented at recent medical meetings, as well as significant opportunities in the competitive landscape.

The estimated primary completion date has been updated to reflect both an increase in patient recruitment (as reported in February 2016 with the inclusion of OS as a co-primary endpoint) and the event-based nature of the trial. As a result, the Company anticipates MYSTIC PFS data in mid-2017 and final OS data at the latest in 2018. MYSTIC also includes several undisclosed interim analyses for OS.

Additionally, the ongoing Phase III NEPTUNE trial will be expanded with local patients to support regulatory submission of durva + treme combination therapy in China for 1st-line NSCLC patients without delaying the anticipated OS data readout in 2018 from the global cohort, which is approaching full recruitment. The Company has also initiated the new Phase III PEARL trial of durvalumab monotherapy versus SoC chemotherapy in 1st-line NSCLC patients whose tumours express PD-L1. The PEARL trial focuses on Asian countries, primarily China, due to the high prevalence of NSCLC in the region.

All amendments will be reflected in updates to clinical trials websites, including clinicaltrials.gov.

Sean Bohen, Executive Vice President, Global Medicines Development and Chief Medical Officer at AstraZeneca, said: "The MYSTIC trial amendments, the NEPTUNE trial expansion and initiation of the new PEARL trial are all designed to enhance our options in 1st-line NSCLC for IO-IO combination as well as for IO monotherapy. We continue to follow the science through both internal and external sources for the benefit of patients and look forward to sharing our first pivotal data in mid-2017."

About MYSTIC
The MYSTIC trial is a randomised, open-label, multi-centre, global, Phase III trial of durvalumab in combination with tremelimumab or durvalumab monotherapy versus SoC platinum-based chemotherapy in 1st-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type advanced or metastatic NSCLC.

About NEPTUNE
The NEPTUNE trial is randomised, open-label, multi-centre, global, Phase III trial of durvalumab in combination with tremelimumab versus SoC platinum-based chemotherapy in 1st-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type advanced or metastatic NSCLC.

About PEARL
The PEARL trial is a randomised, open-label, multi-centre Phase III trial of durvalumab monotherapy versus SoC chemotherapy in 1st-line treatment of patients with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) wild-type advanced or metastatic PDL1-expressing NSCLC. The trial was initiated to determine the efficacy and safety of durvalumab in Asian countries, some of which have the highest current NSCLC burden, with over 1.1 million new cases projected for China alone in 2030.

About Durvalumab
Durvalumab is an investigational human monoclonal antibody directed against programmed death ligand-1 (PD-L1). PD-L1 expression enables tumours to evade detection from the immune system through binding to PD-1 on cytotoxic T lymphocytes. Durvalumab blocks PD-L1 interaction with both PD-1 and CD80 on T cells, countering the tumour’s immune- evading tactics and activating the patient’s immune system to attack the cancer. Durvalumab received FDA Breakthrough Therapy Designation in patients with PD-L1 positive inoperable or metastatic UC in 2016 and Fast Track Designation in 2015 for the treatment of patients with PD-L1 positive metastatic head and neck squamous cell carcinoma. The durvalumab biological license application (BLA) in second-line urothelial carcinoma (UC) has been accepted by the FDA with a PDUFA date in the second quarter of 2017.

AstraZeneca’s Approach to Immuno-Oncology (IO)
IO is a therapeutic approach designed to stimulate the body’s immune system to destroy tumours. At AstraZeneca, and MedImmune, our biologics research and development arm, our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. We believe that IO-based therapies will offer the potential for life-changing cancer treatments for the vast majority of patients.

We are pursuing a comprehensive clinical trial programme that includes durvalumab (PD-L1) monotherapy and durvalumab in combination with tremelimumab (CTLA-4) in multiple tumour types, stages of disease, and lines of therapy, using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine our IO portfolio with small targeted molecules from across our oncology pipeline, and with those of our partners, may provide new treatment options across a broad range of tumours.