Miyarisan Pharmaceutical Co. Ltd.

希望之城开创了生物治疗产品 CBM588 在癌症治疗中的全新应用；最新研究表明，该药物能够调节人体微生物群，有望进一步提升美国食品和药品监督管理局批准的癌症免疫疗法的疗效。 科学家们正在探讨将希望之城颇具前景的 Ⅰ 期临床试验成果，拓展至由 SWOG 癌症研究网络赞助的全球 Ⅱ/Ⅲ 期临床试验中，以期实现更广泛的医疗突破。 来自美国顶尖癌症研究与治疗机构之一的希望之城的医学家们发现，转移性肾癌患者在接受免疫疗法及酶酪氨酸激酶抑制剂治疗期间，口服一种名为 CBM588 的活体生物治疗产品，其健康状况显著改善。近日，《自然医学》（Nature Medicine）期刊上发表了这项 I 期临床试验。 肠道微生物对免疫系统具有调节作用。目前，希望之城的研究人员正携手全球 SWOG 癌症研究网络（SWOG Cancer Research Network），共同设计一项 II/III 期临床试验，旨在评估希望之城所发现的 CBM588 及微生物组调节在晚期癌症患者中的创新应用。希望之城肿瘤内科及治疗研究部的教授兼学术事务副主任 Sumanta Pal 医学博士将担任后续 II/III 期 SWOG 试验的共同领导者。 Sumanta Pal, M.D. “希望之城是首个证明活菌产品能够提升接受免疫治疗的肾癌患者临床治疗效果的机构。CBM588 在癌症治疗领域潜力巨大，因为它有望增强免疫检查点抑制剂的疗效，改善患者的预后，并以有益的方式调节肠道微生物群。”这项新研究的通讯作者、希望之城肿瘤内科医生 Pal 博士表示，“目前正在进行的大规模临床试验对于验证这些益处及应对现有挑战至关重要。如果在这项小型试验及之前与 nivolumab 和 ipilimumab 联合进行的试验中观察到的积极结果得到证实，CBM588 有望成为多种癌症治疗，特别是免疫检查点抑制剂治疗的重要辅助药物。” 根据《美国医学会》网络开放平台发布的一篇文章指出，2018 年约有 44% 的美国癌症患者符合使用检查点抑制剂药物的条件，且这一比例呈上升趋势。 在这项单中心I期临床试验中，30 名转移性肾癌患者被随机分配，接受血管内皮生长因子受体抑制剂卡博替尼（cabozantinib）和靶向免疫疗法药物尼沃鲁单抗（nivolumab）联合或不联合 CBM588 作为一线治疗方案。研究初期，通过粪便样本对患者的肠道微生物组进行了基线分析，并在治疗 13 周后再次进行分析。 目前，希望之城已向 Osel 全球独家授权了用于提高检查点抑制剂治疗癌症（包括转移性肾细胞癌）疗效的 CBM588 这一新型药物。来自 Osel 和 CBM588 制造商米雅利桑制药株式会社（Miyarisan Pharmaceutical Co., Ltd.）的科学家合作进行了这项研究。 迄今为止，许多关于肺癌、黑色素瘤和转移性肾癌等疾病的研究表明，肠道微生物组的组成可以预测癌症患者免疫疗法的疗效。目前的转移性肾细胞癌（肾癌）治疗指南建议新诊断的患者接受双重检查点抑制剂治疗或免疫疗法与酪氨酸激酶抑制剂的联合治疗，但大多数患者在治疗期间仍难逃病情恶化的命运。患者的积极反应往往难以持久，后续治疗大多侧重于缓解病情，而非根治。因此，医学界的科学家们正积极探索将现有策略与无毒性副作用的新疗法相结合的道路，比如通过调节微生物组。 在这项试验中，希望之城的研究人员观察到未分类的反刍球菌属（Ruminococcaceae）数量有所增加，而在最近的研究中，这种微生物与免疫检查点抑制剂临床疗效的改善有关。CBM588 中的丁酸梭菌 MIYAIRI 588 能产生丁酸。丁酸是维护肠道健康的关键物质，同时也是一种广为人知的免疫调节剂。 “虽然微生物组调节尚未纳入标准癌症治疗规程，但它是一个前景广阔的研究领域，有望提升癌症治疗，特别是免疫治疗的疗效。目前的应用主要集中在临床试验阶段，但越来越多的证据表明，基于微生物组的干预措施可能很快成为癌症治疗策略的重要组成部分。”该研究的第一作者、希望之城博士后医学肿瘤学研究员 Hedyeh Ebrahimi 医学博士说道。 希望之城正在加速研究健康肠道与 CAR T 细胞疗法等免疫疗法有效性之间的直接联系。其强化的微生物组项目，涵盖从基础到临床的全面研究，包括研究肠道微生物组在保护移植患者免受康复期间并发症影响方面的作用。 “这项研究再次证明，微生物组在癌症免疫疗法的疗效和毒性方面发挥着重要作用，而且可以有针对性地改善疗效。”希望之城洛杉矶分院和希望之城国家医疗中心院长、Deana & Steve Campbell 首席医师执行杰出讲席教授 Marcel van den Brink 医学博士说道。 《自然医学》期刊上发表的题为“在转移性肾细胞癌中联用卡博替尼和尼沃单抗，并辅以或不辅以活细菌补充的随机 I 期试验”（Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial）的研究，由 Exelixis 公司（项目编号为XL184-IST123）资助。而研究中使用的 CBM588 则是由米雅利桑制药株式会社与 Osel 公司共同提供。 关于希望之城 希望之城的使命是将未来的治愈方法带给今天有所需要的人。希望之城成立于 1913 年，现已发展成为美国最大的癌症研究和治疗机构之一，也是糖尿病和其他危及生命疾病的主要研究中心之一。希望之城的研究为众多突破性癌症药物以及人类合成胰岛素和单克隆抗体奠定了基础。希望之城以美国国家癌症研究所指定的独立性综合癌症中心为核心，为患者带来了独特的综合性护理模式，涵盖了癌症护理、研究和开发、学术和培训以及创新计划。希望之城不断发展的全国性系统包括位于洛杉矶的主院区、遍布南加州的临床护理网点、位于加利福尼亚州橙县的新癌症中心以及位于亚特兰大、芝加哥和凤凰城的治疗网点。希望之城的附属机构包括转化基因组学研究所和 AccessHopeTM 等。 如欲了解更多关于希望之城的更多信息，请通过我们的微信公众号或下方联系方式与我们取得联系。 *本文仅作医疗科普，不代表治疗建议。 希望之城国际癌症研究与治疗中心 现已入驻丁香园官方网站 点击查看详情 >

City of Hope developed a novel use of biotherapeutic product CBM588 in the treatment of cancer; new research suggests the agent adjusts people’s microbiome, possibly leading to enhanced effectiveness of Food and Drug Administration-approved cancer immunotherapies Scientists are in discussions to translate City of Hope’s promising phase 1 trial results into a global phase 2/3 trial sponsored by the SWOG Cancer Research Network LOS ANGELES--(BUSINESS WIRE)-- Physician scientists from City of Hope, one of the largest cancer research and treatment organizations in the United States, found that people with metastatic kidney cancer who orally took a live biotherapeutic product called CBM588 while in treatment with immunotherapy and enzymatic tyrosine kinase inhibitors experienced improved health outcomes. The phase 1 trial was published today in Nature Medicine. Microorganisms in the gut modulate the immune system. City of Hope researchers are now in discussions with the global SWOG Cancer Research Network to design a phase 2/3 trial to assess the City of Hope-identified novel use of CBM588 and microbiome modulation in people with advanced cancer. Sumanta Pal, M.D., professor and vice chair of academic affairs in City of Hope’s Department of Medical Oncology & Therapeutics Research, is slated to be co-leader of the potential phase 2/3 SWOG trial. “We at City of Hope are the first to demonstrate a live bacterial product’s ability to improve clinical outcomes for patients with kidney cancer treated with immunotherapy. CBM588 could be exciting in cancer treatment because of its potential to enhance the efficacy of immune checkpoint inhibitor-based treatment, improve patient outcomes and modulate the gut microbiota in beneficial ways,” said Pal, a City of Hope medical oncologist and corresponding author of the new study. “Ongoing and larger clinical trials are crucial to validate these benefits and address current challenges. If the positive results observed in this small trial and a previous trial with nivolumab and ipilimumab are confirmed, CBM588 could become a valuable supplement in the treatment of various cancers, particularly for patients treated with immune checkpoint inhibitors." An estimated 44% of U.S. patients with cancer in 2018 were eligible for checkpoint inhibitor drugs, according to a JAMA Network Open article that flags the increasing trend of this percentage. In the single-center, phase 1 trial, 30 people with metastatic kidney cancer were randomized to receive cabozantinib, an inhibitor of vascular endothelial growth factor receptor, and targeted immunotherapy nivolumab with or without CBM588 as first-line treatment. Participants’ gut microbiome were analyzed via stool samples in the beginning for a baseline and then 13 weeks into treatment. City of Hope has granted an exclusive worldwide license to Osel for intellectual property on the novel use of CBM588 to enhance the efficacy of checkpoint inhibitors used to treat cancer, including metastatic renal cell carcinoma. Scientists from Osel and Miyarisan Pharmaceutical Co. Ltd, the manufacturer of CBM588, collaborated on the study. To date, many studies on lung cancer, melanoma and metastatic kidney cancer, among other diseases, have shown that the composition of the gut microbiome could predict immunotherapy outcomes for patients with cancer. Current guidelines for metastatic renal cell carcinoma (kidney cancer) recommend that newly diagnosed patients receive either dual checkpoint inhibitor therapy or a combination of immunotherapy and tyrosine kinase inhibitor, but most patients eventually experience disease progression while on treatment. Positive patient outcomes usually do not last, and subsequent treatments are largely palliative rather than curative. So, physician scientists are looking to combine current strategies with new treatments that do not introduce toxic side effects, such as through microbiome modulation. In the trial, City of Hope researchers observed an increase in the abundance of unclassified Ruminococcaceae genera, which has been linked with improved clinical outcomes with immune checkpoint inhibitors in recent studies. Clostridium butyricum MIYAIRI 588, the bacterium in CBM588, produces butyric acid, which is critical for intestinal health and is a well-known immunomodulator. “While not yet part of standard cancer treatment protocols, microbiome modulation is a promising area of research with the potential to enhance the efficacy of cancer therapies, particularly immunotherapies. Current applications are primarily within clinical trials, but the growing body of evidence suggests that microbiome-based interventions may soon become a valuable component of cancer treatment strategies,” said Hedyeh Ebrahimi, M.D, M.P.H., City of Hope postdoctoral medical oncology fellow and first author of the study. City of Hope is accelerating its research on the direct link between a healthy gut and the effectiveness of immune therapies, such as CAR T cell therapy. Its enhanced microbiome program spans from basic to clinical research and includes studying the gut microbiome’s role in protecting transplant patients from complications experienced during their recovery. “This study demonstrates again that the microbiome has an important role in the efficacy and toxicity of cancer immunotherapy and can be targeted to improve outcome,” said Marcel van den Brink, M.D., Ph.D., president of City of Hope Los Angeles and City of Hope National Medical Center, and the Deana and Steve Campbell Chief Physician Executive Distinguished Chair. The Nature Medicine study entitled “Cabozantinib and nivolumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial” was supported by Exelixis Inc. (XL184-IST123). CBM588 was supplied by Miyarisan Pharmaceutical Co., Ltd. and Osel Inc. About City of Hope City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest cancer research and treatment organizations in the U.S. and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center at its core, City of Hope brings a uniquely integrated model to patients spanning cancer care, research and development, academics and training, and innovation initiatives. City of Hope’s growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn. View source version on businesswire.com: Contacts Zen Logsdon 626-409-9367 zlogsdon@coh.org Source: City of Hope View this news release online at: