Bevacizumab

▎药明康德内容团队编辑 GSK今日宣布FIRST-ENGOT-OV44X临床3期试验的主要结果，该试验评估PARP抑制剂Zejula（niraparib）和其PD-1抑制剂Jemperli（dostarlimab）用于一线治疗晚期卵巢癌的疗效与安全性。分析显示，试验达成主要终点无进展生存期（PFS），结果显示在标准护理方案卡铂-紫杉醇化疗和niraparib维持治疗基础上添加dostarlimab，无论是否联合贝伐珠单抗（bevacizumab），都表现出具有统计学意义的显著差异。 FIRST-ENGOT-OV44是一项国际性、双盲、随机的3期试验。该试验旨在评估在标准护理（SOC）铂类化疗和niraparib维持治疗基础上，无论是否联合贝伐珠单抗，添加dostarlimab作为III期或IV期非黏液性上皮性卵巢癌一线治疗的疗效与安全性。 分析显示，试验达成主要终点PFS但关键次要终点总生存期（OS）未达到统计学显著性。进一步的分析正在进行中，相关数据将提交给卫生监管机构并在即将召开的科学会议上公布。试验的安全性和耐受性结果总体上与各单一药物已知的安全性特征一致。 Jemperli是一种能够与PD-1受体结合，并阻断其与配体PD-L1和PD-L2交互作用的抗体。在子宫内膜癌治疗方面，Jemperli已获美国FDA批准，作为在先前接受过含铂疗法后的DNA错配修复缺陷（dMMR）晚期或复发性子宫内膜癌的单药治疗。此外，该疗法并在去年7月获批与卡铂和紫杉醇联合用药，并接续Jemperli作为单药以治疗由美国FDA批准的检测方法确定为dMMR或高微卫星不稳定性（MSI-H）的原发性晚期或复发性子宫内膜癌成人患者。这个月，FDA授予Jemperli突破性疗法认定（BTD），用于治疗dMMR/MSI-H直肠癌。 Zejula则是GSK通过收购TESARO公司所获得的口服、一天一次的PARP抑制剂。PARP抑制剂是通过抑制PARP介导的DNA损伤修复反应（DDR），杀伤癌细胞的靶向疗法。利用“合成致死”原理，它们能够在杀伤癌细胞的同时，最小化对健康细胞的影响。 ▲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 参考资料： [1] GSK announces FIRST trial met its primary endpoint of progression free survival in first line advanced ovarian cancer. Retrieved December 20, 2024 from https://www.gsk.com/en-gb/media/press-releases/gsk-announces-first-trial-met-its-primary-endpoint-of-progression-free-survival-in-first-line-advanced-ovarian-cancer/ 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

LONDON, UK I December 20, 2024 I GSK plc (LSE/NYSE: GSK) today announced headline results from the FIRST-ENGOT-OV44 phase III trial evaluating Zejula (niraparib) and Jemperli (dostarlimab) in first line advanced ovarian cancer. The trial met its primary endpoint of PFS demonstrating a statistically significant difference with the addition of dostarlimab to both standard of care carboplatin-paclitaxel chemotherapy and niraparib maintenance, with or without bevacizumab. Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said : “As part of our focus in gynaecological cancers, we continue to evaluate the potential of this combination and look forward to sharing full results from the trial.” The key secondary endpoint of overall survival (OS) did not meet statistical significance. Further analyses are ongoing and data will be shared with health authorities and presented at an upcoming scientific meeting. The safety and tolerability profile was generally consistent with the known safety profiles of the individual agents. About ovarian cancer Ovarian cancer is the eighth most common cancer in women worldwide. 1 Despite high response rates to platinum-based chemotherapy in the first-line setting, approximately 85% of patients will experience disease recurrence. Once the disease recurs, it is rarely curable, with decreasing time intervals to each subsequent recurrence. 2 About the FIRST trial The FIRST-ENGOT-OV44 trial is an international, double-blind, randomised phase III ENGOT trial sponsored by GSK and led by GINECO, a French cooperative group dedicated to gynecological oncology. FIRST is investigating the addition of dostarlimab to both, standard of care (SOC) platinum-based chemotherapy and niraparib maintenance, with or without bevacizumab, as a first-line treatment of stage III or IV nonmucinous epithelial ovarian cancer. Originally, participants were randomised 1:1:2 into three groups: Arm 1: SOC chemotherapy followed by placebo maintenance; Arm 2: SOC chemotherapy followed by niraparib maintenance; Arm 3: SOC chemotherapy and dostarlimab followed by niraparib and dostarlimab maintenance. Bevacizumab could be added at the investigator’s discretion across all arms. Due to the approvals of PARP inhibitors in the first-line setting, Arm 1 (n=193) was closed and participants were subsequently randomized 1:2 to Arms 2 (n= 385) and 3 (n= 753) only. The primary endpoint is investigator-assessed PFS in Arms 2 and 3. Secondary endpoints include OS, PFS2, time to first and second subsequent therapy. ABOUT GINECO 3 GINECO (Groupe d’Investigateurs National pour l’Etude des Cancers de l’Ovaire et du sein) is the French Cooperative Group in Oncology labelled by INCa (Institut National du Cancer or French NCI) developing and conducting gynecological and metastatic breast cancer clinical trials at the national and international level. The GINECO group was founded in 1993 and is member of international consortia such as ENGOT and GCIG (Gynecologic Cancer InterGroup). About ENGOT 4 The European Network for Gynaecological Oncological Trial (ENGOT) groups is a research network of the European Society of Gynaecological Oncology and was founded in Berlin in October 2007. Currently, ENGOT consists of 21 trial groups from 31 European countries that perform cooperative clinical trials. ENGOT’s ultimate goal is to bring the best treatment to gynaecological cancer patients through the best science and enabling every patient in every European country to access a clinical trial. About Jemperli (dostarlimab) Jemperli , a programmed death receptor-1 (PD-1)-blocking antibody, is the backbone of GSK’s ongoing immuno-oncology-based research and development prgramme. A robust clinical trial programme includes studies of Jemperli alone and in combination with other therapies for gynaecologic, colorectal and lung cancers, as well as where there are opportunities for transformational outcomes. In the US, Jemperli is indicated in combination with carboplatin and paclitaxel, followed by Jemperli as a single agent for the treatment of adult patients with primary advanced or recurrent endometrial cancer. This includes patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) and dMMR/MSI-H tumours. Jemperli is also approved as a single agent for adult patients with dMMR recurrent or advanced endometrial cancer, as determined by a US FDA-approved test, that has progressed on or following a prior platinum-containing regimen in any setting and are not candidates for curative surgery or radiation. Additionally, Jemperli is indicated in the US for patients with dMMR recurrent or advanced solid tumours, as determined by a US FDA-approved test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. The latter indication is approved in the US under accelerated approval based on tumour response rate and durability of response. Continued approval for this indication in solid tumours may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc., under a collaboration and exclusive license agreement signed in March 2014. Under this agreement, GSK is responsible for the ongoing research, development, commercialisation, and manufacturing of Jemperli , and cobolimab (GSK4069889), a TIM-3 antagonist. Important Information for Jemperli in the EU Indications Jemperli is indicated: Refer to the Jemperli EMA Reference information for a full list of adverse events and the complete important safety information in the EU. About Zejula (niraparib) Zejula is an oral, once-daily Poly (ADP-ribose) polymerase (PARP) inhibitor indicated in the US for the maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy; and for the maintenance treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy and who have been selected based on a US FDA-approved companion diagnostic for Zejula . Important Information for Zejula in the EU Indications Zejula is indicated: Refer to the Zejula EMA Reference Information for a full list of adverse events and the complete important safety information in the EU. GSK in oncology Oncology is an emerging therapeutic area for GSK where we are committed to maximising patient survival with a current focus on haematologic malignancies, gynaecologic cancers, and other solid tumours through breakthroughs in immuno-oncology and tumour-cell targeting therapies. About GSK GSK is a global biopharma company with a purpose to unite science, technology, and talent to get ahead of disease together. Find out more at gsk.com. References SOURCE: GlaxoSmithKline