2014年3月12日讯 /生物谷BIOON/ --Oxigene公司3月11日公布了一项随机II期GOG186I研究的积极数据。该项研究调查了Zybrestat（fosbretabulin，CA4P）与罗氏（Roche）畅销药物安维汀（Avastin，通用名：bevacizumab，贝伐单抗）组合疗法用于复发性卵巢癌的治疗。数据表明，与Avastin单药治疗组相比，Zybrestat+Avastin联合治疗组疾病无进展生存期（PFS）显著延长（p＜0.05），达到了研究的主要终点。消息发布后，Oxigene公司股价在盘后交易中飙升1倍多。
GOG186I研究的详细PFS数据将公布于未来的医学会议。该公司称，将对GOG186I研究的患者随访，以便确认Zybrestat+Avastin组合疗法是否能改善总生存期（OS）。
该项研究验证了具有互补机制的血管破坏剂Zybrestat和抗血管生成剂（如Avastin）在卵巢癌中的治疗潜力。Zybrestat和Avastin均能够抑制肿瘤生长所需的血液供应和氧气供应，但作用机制不同。鉴于当前复发性卵巢癌群体对新治疗方案的重大需求，这一有前途的组合疗法，值得开展III期进一步评价。
目前，在美国，Avastin还未获批用于卵巢癌的治疗，但在其他一些国家已获批用于卵巢癌适应症。
GOG186I研究由非营利组织妇科肿瘤学组（GOG）开展，由美国国家癌症研究所（NCI）癌症疗法评估项目（CTEP）资助，这是首个将一种抗血管生成治疗药物与一种血管破坏剂进行联合用药的随机研究，而且没用使用任何细胞毒性药物化疗。
关于Zybrestat：
Zybrestat（fosbretabulin tromethamine）是由Oxigene公司开发的名为血管破坏剂（vascular disrupting agents）的新一类小分子药物，通过与血管内皮细胞的细胞骨架蛋白相互作用，Zybrestat选择性作用于肿瘤中的血管，并破坏这些血管，从而使肿瘤失去氧气供给而凋亡。该药已表现出对未分化甲状腺癌、卵巢癌及其他各种实体瘤的治疗潜力。
此前，欧洲药品管理局（EMA）于2013年授予Zybrestat治疗卵巢癌的孤儿药地位。（生物谷Bioon.com）
英文原文：OXiGENE Announces Positive Topline Results From Randomized Phase 2 Study GOG186I of ZYBRESTAT(R) in Combination With Avastin(R) for Recurrent Ovarian Cancer
Trial Achieves Primary Efficacy Endpoint of a Statistically Significant Increase in Progression-Free Survival
SOUTH SAN FRANCISCO -- OXiGENE, Inc.OXGN +136.78% , a clinical-stage biopharmaceutical company developing novel therapeutics to treat cancer, today announced positive results from a randomized Phase 2 clinical trial evaluating Avastin (bevacizumab) with or without ZYBRESTAT (fosbretabulin; CA4P) to treat patients with recurrent ovarian cancer. The study, known as Gynecologic Oncology Group protocol 186I, met its primary endpoint of a statistically significant increase in progression-free survival (p-value less than 0.05; hazard ratio 0.685) for the combination as compared to bevacizumab alone.
The Phase 2 study is being conducted by the GOG under the sponsorship of the Cancer Therapy Evaluation Program (CTEP) of the National Cancer Institute (NCI). It is the first and currently only randomized trial to test an antiangiogenic therapeutic agent combined with a vascular disrupting agent, without including any cytotoxic chemotherapy.
"These findings validate both the novel approach and the complementary mechanisms of combining the vascular disrupting agent fosbretabulin and an antiangiogenic agent like bevacizumab in patients with ovarian cancer," said Bradley J. Monk, M.D., FACS, FACOG, principal investigator for the trial, and professor and director, Division of Gynecologic Oncology and Department of Obstetrics and Gynecology at the University of Arizona Cancer Center. "This promising combination warrants further evaluation particularly given the significant need for new treatment options in relapsed ovarian cancer."
As previously reported, the GOG protocol 186I enrolled 107 patients with platinum-sensitive and -resistant recurrent ovarian cancer at 67 clinical sites in the U.S. Patients were randomized 1:1 into one of two treatment arms: one arm received Avastin, and the second arm received Avastin plus ZYBRESTAT. Both therapies were administered intravenously every three weeks and patients were treated until disease progression or until adverse effects prohibited further therapy.
Secondary endpoints in the study include safety, objective response rate (measured according to RECIST criteria) and overall survival. Patients receiving the combination of ZYBRESTAT and Avastin achieved a higher objective response rate, which was not statistically significant. All patients will continue to be followed for overall survival. Consistent with prior clinical experience with ZYBRESTAT, patients in the combination arm experienced a higher incidence of hypertension compared to the control arm. All cases of hypertension were managed with antihypertensive treatments, as specified in the study protocol. It is expected that the full study results will be submitted for presentation at a future scientific meeting.
For this study, ZYBRESTAT is provided to CTEP under a Cooperative Research and Development Agreement (CRADA) with OXiGENE and bevacizumab is being provided as an investigational agent under a CRADA with Genentech. Bevacizumab is not approved to treat women with ovarian cancer in the U.S.; however, it is approved in other countries for treatment of ovarian cancer.
"We are very excited about these positive results and greatly appreciate all the patients who enrolled in this study and the support, resources and commitment of GOG and CTEP to conduct this important program," said Peter Langecker, M.D., Ph.D., chief executive officer of OXiGENE. "ZYBRESTAT is the first vascular disrupting agent to show a statistically significant progression-free survival benefit, and we are evaluating next steps to advance this combination to patients in need."
About ZYBRESTAT
ZYBRESTAT (fosbretabulin tromethamine/combretastatin-A4 phosphate / CA4P) is OXiGENE's lead vascular disrupting agent (VDA) product candidate, and is currently being evaluated as a treatment for solid tumors. ZYBRESTAT exerts its antitumor effects through the validated therapeutic mechanism of tumor blood supply deprivation. By selectively affecting and disabling tumor vasculature, ZYBRESTAT reduces the blood supply necessary for tumor growth and survival. The resulting oxygen starvation and build-up of tumor metabolic by-products causes the cancer cells within the central core of the tumor to die.
About the Gynecologic Oncology Group
The Gynecologic Oncology Group (GOG) is a not-for-profit 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. The GOG is one of the National Cancer Institute's funded cooperative groups. The GOG is the only group that focuses its research on women with pelvic malignancies, such as cancer of the ovary, uterus, and cervix. The GOG is multi-disciplinary in its approach to clinical trials, and includes gynecologic oncologists, medical oncologists, pathologists, radiation oncologists, nurses, statisticians, basic scientists, quality of life experts, data managers, and administrative personnel.
About OXiGENE
OXiGENE is a biopharmaceutical company developing novel therapeutics to treat cancer. The Company is focused on developing vascular disrupting agents (VDAs), which are compounds that selectively disrupt abnormal blood vessels associated with solid tumor survival and progression. The Company's lead clinical product candidate, ZYBRESTAT, is in development for solid tumors. OXi4503, its second-generation product candidate, is in development for acute myeloid leukemia (AML). OXiGENE is dedicated to leveraging its intellectual property and therapeutic development expertise to bring life-extending and life-enhancing medicines to patients.
关键词：Oxigene,Zybrestat,Avastin,卵巢癌
信息来源:生物谷
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