On January. 20, 2017 Mateon Therapeutics, Inc. (OTCQX:MATN), a biopharmaceutical company developing vascular disrupting agents (VDAs) for the treatment of orphan oncology indications, reported the presentation of final data from Study OX4218 in patients with neuroendocrine tumors (NETs) at a poster session at the ASCO (Free ASCO Whitepaper) Gastrointestinal Cancers Symposium being held today in San Francisco.

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Study OX4218 was a multi-center, open label, phase 2 clinical trial to investigate the safety and activity of combretastatin A4-phosphate (CA4P) in the treatment of well-differentiated, low-to-intermediate-grade unresectable, recurrent or metastatic pancreatic or gastrointestinal neuroendocrine tumors/carcinoid (PNETs or GI-NETs) with elevated biomarkers. Following patients’ completion of Study OX4218, patients were eligible to enroll in Study OX4219, a long term extension study, if they achieved a biomarker or symptom response. In OX4218 patients were treated with CA4P 60 mg/m2 on Days 1, 8, and 15 of a 21-day cycle for 3 cycles, and in OX4219 patients received CA4P maintenance on Day 1 of a 21-day cycle until disease progression or up to one year.

A total of 18 patients were enrolled in OX4218. One patient (6%) experienced significant symptomatic improvement as measured by ECOG Status and had a partial response per investigator-assessed RECIST and an additional 7 patients (39%) had stable disease. In addition, a majority of patients (53%) experienced an improvement in patient-reported quality of life. A statistically significant mean change in biomarkers from baseline, the primary endpoint of the study, was not achieved in OX4218 due to the small sample size along with a high intra- and inter-patient variability observed in the biomarkers. A total of 7 patients were enrolled in OX4219, of which 5 patients (71%) had stable disease, including one that continued for 14 months. The partial response and stable disease analyses, as well as other measures from the trial, suggest that CA4P monotherapy has activity in this indication.

"The results of OX4218 and OX4219 confirm that CA4P monotherapy has efficacy in the indications studied, as we have seen with the investigational drug in a number of other monotherapy trials," said William D. Schwieterman, M.D., President and Chief Executive Officer of Mateon. "However, we believe that the efficacy of CA4P only becomes compelling when it is used in combination with an anti-angiogenic agent, due to the complementary mechanisms of action for the two agents. Based on the evidence of efficacy observed in this trial, plus an understanding of the benefits of combination therapy, a lead investigator in this trial is sponsoring a 20 patient study in NETs using CA4P in combination with everolimus (AFINITOR, marketed by Novartis), an anti-angiogenic agent which is already approved and commonly used in this indication."

Overall CA4P monotherapy was well tolerated. Treatment related adverse events were reported in 77% of subjects. The most common Grade 3-5 AEs ( > 10%) included: anemia, abdominal pain, fatigue, hypertension, and ALT and AST increases. One Grade 5 adverse event, carcinoid syndrome, was reported and attributed to the underlying disease.

On January 20, 2017 Bayer reported that the Japanese Ministry of Health, Labour and Welfare (MHLW) has granted priority review to Bayer Yakuhin, Ltd., Osaka, Japan, for regorafenib in the second-line treatment of patients with unresectable hepatocellular carcinoma (HCC) (Press release, , JAN 20, 2017, View Source;sessionID=1485224246 [SID1234517530]). Regorafenib was submitted for marketing approval in HCC in Japan in October 2016. The MHLW grants priority review to medicines on the basis of their clinical usefulness and severity of the disease. Regorafenib is already approved under the brand name Stivarga in many countries, including Japan, to treat metastatic colorectal cancer and unresectable and/or metastatic gastrointestinal stromal tumors.

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"Liver cancer is one of the leading cancer-related causes of death in Japan. Nexavar as the first and only approved systemic treatment for HCC has been a major advance in this field, but effective second-line treatment options are urgently needed for patients", said Dr. Joerg Moeller, member of the Executive Committee of Bayer AG’s Pharmaceutical Division and Head of Development. "We welcome the priority review for regorafenib in Japan as it supports our efforts to make the compound available as early as possible in the second-line setting for HCC in Japan."

The regulatory submission for regorafenib is based on data from the international, multicenter, placebo-controlled Phase III RESORCE [REgorafenib after SORafenib in patients with hepatoCEllular carcinoma] trial. The trial investigated regorafenib in patients with unresectable hepatocellular carcinoma (HCC) whose disease had progressed during treatment with sorafenib (Nexavar) tablets. Results showed that regorafenib significantly improved overall survival (OS) compared to placebo (HR 0.63; 95% CI 0.50-0.79; p<0.001), which over the trial period represents a 37 percent reduction in the risk of death for patients who received regorafenib plus best supportive care (BSC) compared to patients treated with placebo plus BSC. The median OS was 10.6 months in patients treated with regorafenib, compared to 7.8 months in patients who received placebo plus BSC. The safety and tolerability was generally consistent with the known profile of regorafenib, with no clinically meaningful differences in health-related quality of life (HRQoL) between the regorafenib and placebo plus BSC groups. Data from the study were first presented at the 18th World Congress on Gastrointestinal Cancer (WCGC) in June 2016 and published online on December 5, 2016 in the peer-reviewed journal The Lancet.

Regorafenib has also been submitted to the regulatory authorities in the US and EU for the treatment of second-line HCC.

About the RESORCE trial
The Phase III RESORCE [REgorafenib after SORafenib in patients with hepatoCEllular carcinoma] clinical trial enrolled 573 patients whose disease had progressed during treatment with sorafenib. Patients were randomized in a 2:1 ratio to receive either regorafenib or placebo plus best supportive care.

Patients received 160 mg regorafenib once daily or placebo, for 3 weeks on/1week off, with 28 days constituting one full treatment cycle. The primary endpoint of the study was overall survival, and secondary endpoints were time to progression, progression-free survival, objective tumor response rate and disease control rate. Health-related quality of life was assessed by the FACT-Hep and EQ-5D questionnaires. Safety and tolerability were also continuously monitored.

About Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the most common form of liver cancer and represents approximately 70-85 percent of liver cancer worldwide. Liver cancer is the sixth most common cancer in the world and the second leading cause of cancer-related deaths globally. More than 780,000 cases of liver cancer are diagnosed worldwide each year (52,000 in the European Union, 501,000 in the Western Pacific region and 30,000 in the United States) and the incidence rate is increasing. In 2012, approximately 746,000 people died of liver cancer including approximately 48,000 in the European Union, 477,000 in the Western Pacific region and 24,000 in the United States.

About Regorafenib (Stivarga)
Regorafenib is an oral multi-kinase inhibitor that potently blocks multiple protein kinases involved in tumor angiogenesis (VEGFR1, -2, -3, TIE2), oncogenesis (KIT, RET, RAF-1, BRAF), metastasis (VEGFR3, PDGFR, FGFR) and tumor immunity (CSF1R).

Regorafenib is approved under the brand name Stivarga in more than 90 countries worldwide, including the U.S., countries of the EU and Japan for the treatment of metastatic colorectal cancer (mCRC). The product is also approved in over 80 countries, including the U.S., countries of the EU and Japan, for the treatment of metastatic gastrointestinal stromal tumors (GIST). In the EU, Stivarga is indicated for the treatment of adult patients with mCRC who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-based chemotherapy, an anti-VEGF therapy and an anti-EGFR therapy, as well as for the treatment of adult patients with unresectable or metastatic GIST who progressed on or are intolerant to prior treatment with imatinib and sunitinib.

Regorafenib is a compound developed by Bayer. In 2011, Bayer entered into an agreement with Onyx, now an Amgen subsidiary, under which Onyx receives a royalty on all global net sales of regorafenib in oncology.

On January 20, 2017 Polaris Group reported that the first patient has been dosed in its phase 1 trial of ADI‑PEG 20 in combination with low-dose cytarabine for the treatment of acute myeloid leukemia (AML) in older patients (Press release, Polaris Pharmaceuticals, JAN 20, 2017, View Source [SID1234526287]). In addition to a global phase 2/3 study in malignant plural mesothelioma featuring ADI‑PEG 20 in combination with pemetrexed and cisplatin, Polaris Group is currently conducting multiple phase 1 clinical trials, including ADI‑PEG 20 in combination with pemetrexed and cisplatin in non-small cell lung carcinoma, glioblastoma, and uveal melanoma, in combination with gemcitabine and paclitaxel in pancreatic cancer and in combination with FOLFOX in hepatocellular carcinoma, gastric cancer, and colorectal cancer.

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"We hope that the addition of ADI‑PEG 20, which has a different mechanism of action than cytarabine, will result in both safety and added efficacy", said John Bomalaski, M.D., Executive Vice President, Medical Affairs at Polaris Pharmaceuticals, Inc.

About ADI‑PEG 20

ADI‑PEG 20 is a biologic being developed by Polaris Group to treat cancers carrying a major metabolic defect that renders them unable to internally synthesize arginine. Because arginine is essential for protein synthesis and survival of cells, these cancer cells become dependent upon the external supply of arginine to survive and grow. ADI‑PEG 20 is designed to deplete the external supply of arginine, causing arginine-dependent cancer cells to die while leaving the patient’s normal cells unharmed. Multiple cancers have been reported to have a high degree of arginine-dependency and can potentially be treated with ADI‑PEG 20.

On January 20, 2017 FibroGen, Inc. (Nasdaq:FGEN) reported that updated results from an ongoing clinical study of pamrevlumab (FG-3019) in combination with standard-of-care chemotherapy in patients with locally advanced pancreatic ductal adenocarcinoma (PDAC) were presented in a poster session during the ASCO (Free ASCO Whitepaper) 2017 Gastrointestinal Cancers Symposium in San Francisco (Press release, FibroGen, JAN 20, 2017, View Source;p=IROL-news&nyo=0 [SID1234517531]). Pamrevlumab is a fully human monoclonal therapeutic antibody that inhibits connective tissue growth factor (CTGF), a common factor in chronic fibrotic and proliferative disorders.

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"I am very encouraged by these additional results from this clinical trial of pamrevlumab evaluated in combination with standard-of-care chemotherapy in patients with locally advanced pancreatic ductal adenocarcinoma," said Vincent J. Picozzi, Jr., M.D., Director of the Pancreas Center, Virginia Mason Hospital & Seattle Medical Center, and principal investigator. "Based on our participation in this trial, and a previous clinical study (FGCL- MC3019-028), I believe pamrevlumab has the potential to provide meaningful benefit for pancreatic cancer patients with locally advanced and/or metastatic disease."

Of the 33 subjects enrolled to date:

Twenty-two have been randomized to pamrevlumab plus chemotherapy, 10 remain on treatment
– Three discontinued treatment due to complications not related to pamrevlumab, and nine completed treatment
– Seven subjects who completed treatment met protocol defined criteria eligible for tumor resection and were considered operable following treatment. Three subjects had complete tumor removal (R0), and one subject had microscopic tumor remaining after surgery (R1)
Of the 11 subjects randomized to chemotherapy alone, five subjects discontinued treatment due to various reasons, and six subjects completed treatment
– Of the six subjects who received chemotherapy alone, one subject met protocol defined criteria eligible for tumor resection and had a complete tumor removal (R0)
Differences in overall survival (OS) between subjects treated with and without pamrevlumab look encouraging
There were no complications from laparoscopy or biopsies that were clinically significant or delayed dosing, and, to date, there have been no safety imbalances between treatment arms.
In this open-label, randomized study, pamrevlumab in combination with gemcitabine and nab-paclitaxel is compared to chemotherapy alone for the treatment of patients with locally advanced pancreatic ductal adenocarcinoma who have failed resection scoring and were characterized as inoperable assessed by histology, CT scans, and laparoscopy. Subjects are randomized to six cycles of chemotherapy with gemcitabine and nab-paclitaxel, with or without pamrevlumab. The study has enrolled 33 patients, and is targeted to enroll up to 42 subjects.

About Pancreatic Ductal Adenocarcinoma and Connective Tissue Growth Factor

Pancreatic ductal adenocarcinoma (PDAC), or pancreatic cancer, is the fourth leading cause of cancer deaths in the United States. According to the National Cancer Institute, in 2016, there were approximately 53,000 new cases of pancreatic cancer projected in the United States alone. Pancreatic cancer is aggressive and typically not diagnosed until it is largely incurable. Most patients are diagnosed after the age of 45, and overall five-year survival is about 7%, due to many factors, including advanced stage at diagnosis and limited response to currently available therapies (View Source). PDAC tumors often exhibit a high degree of desmoplasia, characterized by extensive connective tissue stroma and elevated levels of Connective Tissue Growth Factor (CTGF). Cancer-stroma interactions affect tumorigenesis, angiogenesis, resistance to therapy and metastatic spread of tumor cells. CTGF is overexpressed in PDAC and facilitates local desmoplasia, tumor progression and metastasis in animal models.

About Pamrevlumab

Pamrevlumab (FG-3019) is an investigational therapeutic antibody developed by FibroGen to inhibit the activity of CTGF, a common factor in chronic fibrotic and proliferative disorders characterized by persistent and excessive scarring that can lead to organ dysfunction and failure. FibroGen is currently conducting clinical studies of pamrevlumab in idiopathic pulmonary fibrosis, pancreatic cancer, and Duchenne muscular dystrophy.

In desmoplastic, or fibrotic, cancers such as pancreatic cancer, CTGF in the extensive fibrous stroma associated with the tumor promotes abnormal proliferation of stromal cells and tumor cells. Studies in a transgenic mouse model of pancreatic cancer indicate that treatment with pamrevlumab in combination with chemotherapy may enhance the efficacy of chemotherapy and improve survival.

On January 19, 2017 Celsion Corporation reported that it will present two posters at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) – Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Clinical Immuno-Oncology Symposium being held from February 23 – 25, 2017 in Orlando, FL (Press release, Celsion, JAN 19, 2017, View Source [SID1234517449]). The symposium will focus on the latest clinical and translational research in immuno-oncology and the implications for clinical care. The first poster will report clinical results from the 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. The second poster will report translational data from the OVATION Study and previous GEN-1 clinical trials. The posters will be presented by Khursheed Anwer, Ph.D., Celsion’s executive vice president and chief science officer.

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Poster Presentation details:

Title: Phase I study and activity of formulated IL-12 plasmid administered intraperitoneally in combination with standard neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer
Date and Time: Poster Session A – February 23, 2017 (11:30 am – 1:00 pm ET; 5:30 pm to 6:30 pm ET)
Poster Number: 155

Title: Immunological changes following intraperitoneal administration of a formulated IL-12 plasmid in combination with standard neoadjuvant chemotherapy in patients with newly diagnosed advanced stage ovarian cancer
Date and Time: Poster Session A – February 23, 2017 (11:30 am – 1:00 pm ET; 5:30 pm to 6:30 pm ET)
Poster Number: 156

"Our hypothesis is that GEN-1 plus neoadjuvant chemotherapy treatment will reprogram the tumor immune microenvironment towards a potent antitumor immune response," said Dr. Anwer. "The available data demonstrate highly relevant immunological changes in the tumor immune environment, such as tumor infiltration of cytotoxic T-cell lymphocytes and a reduction of certain immunosuppressive signals, which supports the immune activating role of GEN-1 in this patient population. Evidence of immune activation following the treatment is also supported by increases in IFN-g, a potent mediator of the anti-tumor immune response associated with IL-12 action. We are excited to present at the ASCO (Free ASCO Whitepaper)-SITC symposium, and look forward to sharing the impressive clinical and translational results with the scientific community."

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. 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.