使患者总生存期翻2.5倍的免疫联合疗法；4周内减重超15斤的GLP-1/GIP受体双重调节剂... | 一周盘点

2023-07-02

免疫疗法细胞疗法临床结果临床1期

▎药明康德内容团队编辑本期看点1. GLP-1/GIP受体双重调节剂CT-388用于治疗超重和肥胖成人的早期临床结果亮眼，每周给药一次，患者的体重在4周内减轻15.4斤。2. 肿瘤免疫治疗新药Galinpepimut-S（GPS）联用PD-1抑制剂纳武利尤单抗 PD-1抑制剂纳武利尤单抗治疗恶性胸膜间皮瘤，患者的中位总生存期（OS）约为接受标准治疗的患者的2.5倍。3. 治疗复发或难治性急性髓系白血病的即用型嵌合抗原受体（CAR）自然杀伤（NK）细胞疗法使超过半数患者达到完全缓解（CR）。药明康德内容团队整理CT-388 CT-388：公布1/2期临床试验数据Carmot Therapeutics公布了其GLP-1/GIP受体双重调节剂CT-388用于治疗超重和肥胖成人的1/2期临床试验的积极数据。结果显示，CT-388 CT-388的耐受性良好，药代动力学特征支持每周一次的给药频率，最常见的不良事件与胃肠道相关，与肠促胰岛素类别药物一致。在CT-388 CT-388用药后，患者的体重在4周内减轻了8.4%（15.4斤），同时腰围和臀围缩小，胰岛素敏感性标志物（HOMA-IR）得到改善。该研究的初步概况表明，肥胖患者可能受益最多，因为患者的耐受性更强，体重减轻更多。Galinpepimut-S：公布1期临床试验数据SELLAS Life Sciences Group公司公布了其靶向WT1蛋白的潜在“first-in-class”肿瘤免疫治疗新药Galinpepimut-S联用PD-1抑制剂纳武利尤单抗 PD-1抑制剂纳武利尤单抗用于治疗恶性胸膜间皮瘤患者的1期临床数据，这些患者的肿瘤普遍表达WT1。该药由4条多肽链构成，抗原表位多达25个，适用于全球范围内绝大多数人类白细胞组织相容性抗原（HLA）类型，能够激发自身免疫系统对WT1抗原强烈的免疫反应。研究结果显示，该试验达到了安全性和疗效的主要终点，并观察到了联合疗法的临床活性和患者生存率的提高。接受联合疗法的患者的中位OS为70.3周，最后一次随访时有40%的患者存活，而接受标准治疗的复发/难治性患者的中位OS约为28周。根据RECIST标准评估的该联合疗法的疾病控制率（DCR）为30%。此外，没有观察到剂量限制性毒性。NKX101：公布1期临床试验的新数据Nkarta公司更新了其CAR-NK细胞候选疗法NKX101治疗复发或难治性急性髓系白血病患者的临床进展。NKX101是一款同种异体的即用型NK细胞疗法，使用从健康供体中获得的外周血NK细胞，并利用生物工程添加CAR。NKX101的CAR靶向肿瘤表面的NKG2D配体。NKG2D是NK细胞的关键性激活受体，其配体在癌症细胞中过度表达。除了CAR之外，NKX101还表达与细胞膜结合的IL-15，用于增强细胞的持久性和活性。此次更新的数据显示，在使用一周三次的NKX101治疗前采用氟达拉滨/阿糖胞苷清除淋巴细胞，在急性髓系白血病患者（包括一些具有高风险特征的患者）中具有令人鼓舞的抗白血病活性，6名患者中有4名达到CR，其中2名CR患者的微小残留病（MRD）为阴性，1名患者通过额外周期的治疗加深了MRD阴性CR伴不完全的血液恢复（CRi）患者的缓解。此外，NKX101在不同的剂量水平下和淋巴细胞清除疗法中均有良好的耐受性。BB-301：IND申请获得FDA许可BB-301是Benitec Biopharma公司开发的用于治疗眼咽肌营养不良（Oculopharyngeal Muscular Dystrophy）的沉默和取代基因疗法。该疗法利用一种新型的、经过改良的AAV9载体，表达一种独特的、单一的双功能构建体，从而能够促进密码子优化的PABPN1基因和两个针对PABPN1突变体的siRNA的共同表达。这两个siRNA被塑造成microRNA骨架，以抑制有缺陷的PABPN1突变体的表达，同时允许表达经过密码子优化的PABPN1基因，用PABPN1蛋白的功能性版本取代突变体。FPI-1434：公布1期临床试验的中期数据Fusion Pharmaceuticals公司公布了其放射免疫偶联物FPI-1434用于治疗实体肿瘤的1期临床试验的中期数据。FPI-1434结合了抗体的精确定位和发射α粒子的医用同位素的效力，可以特异性地攻击和根除多种肿瘤类型的癌细胞。它的一端能靶向IGF-1R，IGF-1R在癌细胞表面广泛存在，这一抗体能很好地靶向肿瘤，并被内吞入癌细胞内。它的另一端是锕225（225Ac），这种锕的同位素能释放出α粒子，在癌细胞内造成DNA双链的大量断裂，引起癌细胞死亡。此次公布的结果显示，在施用放射性标记的FPI-1434之前预先施用冷抗体（无同位素的裸IGF-1R抗体），有望通过将更多的活性药物推向肿瘤部位而大大增强治疗指数，与只用热剂（单独使用FPI-1434）相比，安全性有所改善。此外，在预先施用冷抗体的情况下，只需注射辐射量的一小部分，就能达到与只用热剂的队列相当的暴露量。结果显示，冷/热方案中15 kBq/kg的药代动力学特征与40 kBq/kg的纯热方案相当，其安全性使其迄今可进行多达5个周期的治疗。此外，两名此前接受过大量治疗的患者在接受了3个和5个周期的治疗后实现了持久的疾病稳定。该公司正在继续评估队列2中更高剂量水平的冷/热方案，预计将在2023年年底左右公布这些结果。FB101：公布1期临床试验数据Freya Biosciences公司公布了其在研阴道微生物免疫疗法FB101用于治疗无症状阴道生态失调女性的1期临床试验的积极顶线结果。结果表明，连续三天在阴道内使用FB101后，患者阴道菌群失调的问题得到了解决，菌群从失调状态迅速转变为以乳酸菌为主的阴道微生物群，并保持了8周以上。此外，一半的妇女建立了FB101乳酸菌的定植（由菌种水平的移植分析确定），并观察到了炎症标志物的变化。该公司后续计划探索FB101用于提高体外受精的成功率并改善生育结果。大家都在看▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息参考资料（可上下滑动查看）[1] Benitec Biopharma Receives FDA Clearance of the IND for BB-301 for the Treatment of Oculopharyngeal Muscular Dystrophy. Retrieved June 30, 2023, from https://www.globenewswire.com/news-release/2023/06/26/2694388/0/en/Benitec-Biopharma-Receives-FDA-Clearance-of-the-IND-for-BB-301-for-the-Treatment-of-Oculopharyngeal-Muscular-Dystrophy.html[2] portage biotech announces first patient dosed in phase 1a trial of port-6 in select solid tumors. Retrieved June 30, 2023, from https://ir.portagebiotech.com/news-releases/news-release-details/portage-biotech-announces-first-patient-dosed-phase-1a-trial[3] cystetic Medicines Initiates Phase 1 Clinical Trial of a Molecular Prosthetic for Cystic Fibrosis. Retrieved June 30, 2023, from https://www.prnewswire.com/news-releases/cystetic-medicines-initiates-phase-1-clinical-trial-of-a-molecular-prosthetic-for-cystic-fibrosis-301863104.html[4] Freeline Announces First Patient Dosed with Its Novel Gene Therapy Candidate for Gaucher Disease and Unveils Research Program in GBA1-linked Parkinson’s Disease. Retrieved June 30, 2023, from https://www.freeline.life/investors/newsroom/freeline-announces-first-patient-dosed-with-its-novel-gene-therapy-candidate-for-gaucher-disease-and-unveils-research-program-in-gba1-linked-parkinson-s-disease/[5] Inozyme Pharma Announces Dosing of First Infant with ENPP1 Deficiency in a Phase 1b Trial of INZ-701. Retrieved June 30, 2023, from https://investors.inozyme.com/news-releases/news-release-details/inozyme-pharma-announces-dosing-first-infant-enpp1-deficiency[6] IAVI Starts First-in-Human Phase I Clinical Trial of Single-Dose Sudan Virus Vaccine Candidate. Retrieved June 30, 2023, from https://www.accesswire.com/763800/IAVI-Starts-First-in-Human-Phase-I-Clinical-Trial-of-Single-Dose-Sudan-Virus-Vaccine-Candidate[7] Regulus Therapeutics Announces First Patient Dosed in Second Cohort of Phase 1b Multiple-Ascending Dose (MAD) Clinical Trial of RGLS8429 for the Treatment of Autosomal Dominant Polycystic Kidney Disease (ADPKD) . Retrieved June 30, 2023, from https://www.prnewswire.com/news-releases/regulus-therapeutics-announces-first-patient-dosed-in-second-cohort-of-phase-1b-multiple-ascending-dose-mad-clinical-trial-of-rgls8429-for-the-treatment-of-autosomal-dominant-polycystic-kidney-disease-adpkd-301863810.html[8] HARPOON THERAPEUTICS ANNOUNCES COMPLETION OF PLANNED PATIENT ENROLLMENT IN PHASE 1 STUDY OF HPN217 IN RELAPSED/REFRACTORY MULTIPLE MYELOMA. Retrieved June 30, 2023, from https://ir.harpoontx.com/news-releases/news-release-details/harpoon-therapeutics-announces-completion-planned-patient[9] First-in-Man trial for Lobe's proprietary stabilized psilocin analogue All subjects dosed with no significant adverse events to date. Retrieved June 30, 2023, from https://s3.amazonaws.com/b2icontent.irpass.cc/2565/rl119662.pdf[10] Microba Commences Phase I Clinical Trial for IBD Therapeutic. Retrieved June 30, 2023, from https://www.businesswire.com/news/home/20230627143323/en/[11] Carisma Therapeutics Announces First Patient Dosed in Phase 1 Study of CT-0508 in Combination with KEYTRUDA® (pembrolizumab) in Patients with HER2 Overexpressing Solid Tumors. Retrieved June 30, 2023, from https://www.prnewswire.com/news-releases/carisma-therapeutics-announces-first-patient-dosed-in-phase-1-study-of-ct-0508-in-combination-with-keytruda-pembrolizumab-in-patients-with-her2-overexpressing-solid-tumors-301865175.html[12] Kyverna Therapeutics Announces First Patient Enrolled in Phase 1 Clinical Trial of CD19 CAR T-cell Therapy for Lupus Nephritis in the U.S. Retrieved June 30, 2023, from https://www.prnewswire.com/news-releases/kyverna-therapeutics-announces-first-patient-enrolled-in-phase-1-clinical-trial-of-cd19-car-t-cell-therapy-for-lupus-nephritis-in-the-us-301866433.html[13] Carmot Therapeutics Highlights Clinical Data from its Pipeline of Treatments for Obesity and Diabetes at the 83rd American Diabetes Association Scientific Sessions. Retrieved June 30, 2023, from https://carmot.us/carmot-therapeutics-highlights-clinical-data-from-its-pipeline-of-treatments-for-obesity-and-diabetes-at-the-83rd-american-diabetes-association-scientific-sessions/[14] Fusion Pharmaceuticals to Present Interim Data from Phase 1 Trial of FPI-1434 in Patients with Solid Tumors Expressing IGF-1R. Retrieved June 30, 2023, from https://www.prnewswire.com/news-releases/fusion-pharmaceuticals-to-present-interim-data-from-phase-1-trial-of-fpi-1434-in-patients-with-solid-tumors-expressing-igf-1r-301862952.html[15] Freya Biosciences Announces Positive Topline Clinical Trial Results for FB101 in Women with Asymptomatic Vaginal Dysbiosis. Retrieved June 30, 2023, from https://www.businesswire.com/news/home/20230627892527/en/[16] NKARTA UPDATES CLINICAL PROGRESS OF CAR-NK CELL THERAPY NKX101 FOR PATIENTS WITH RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA. Retrieved June 30, 2023, from https://ir.nkartatx.com/news-releases/news-release-details/nkarta-updates-clinical-progress-car-nk-cell-therapy-nkx101[17] SELLAS Life Sciences Reports Positive Data in Completed Phase 1 Study of Galinpepimut-S Combined with Opdivo® in Advanced Malignant Pleural Mesothelioma. Retrieved June 30, 2023, from https://www.globenewswire.com/news-release/2023/06/28/2696184/0/en/SELLAS-Life-Sciences-Reports-Positive-Data-in-Completed-Phase-1-Study-of-Galinpepimut-S-Combined-with-Opdivo-in-Advanced-Malignant-Pleural-Mesothelioma.html 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新