Nemvaleukin Alfa

The therapy also reduced the amount of time patients spend receiving chemotherapy treatment by 49.7% compared with IV Keytruda. Credit: Shutterstock / SamaraHeisz5. MSD’s subcutaneous (SC) Keytruda (pembrolizumab) has shown non-inferior pharmacokinetics (PK) to the intravenous (IV) version of the company’s blockbuster therapy in a pivotal trial. The ongoing, randomised, open-label Phase III 3475A-D77 trial (NCT05722015) investigating SC Keytruda delivered every six weeks met its primary endpoint demonstrating non-inferior PK when administered with chemotherapy with a median injection time of two minutes in patients with metastatic non-small cell lung cancer (NSCLC). The therapy also reduced the amount of time patients spend receiving chemotherapy treatment by 49.7% compared with IV Keytruda. At the same time, secondary objectives comparing objective response rate (ORR), progression-free survival (PFS) and duration of response (DOR) were consistent with intravenous (IV) Keytruda chemotherapy. Based on this data, the US Food and Drug Administration (FDA) has accepted a biologics licence application (BLA) for SC Keytruda. A Prescription Drug User Fee Act (PDUFA) date has been set for 23 September. The European Medicines Agency (EMA) has validated an extension application for the SC version of the therapy. Reducing the amount of time chemotherapy patients spend receiving treatment has a number of ancillary benefits, including a reduction in time spent by clinicians working with a single patient. Results from the 3475A-D77 trial saw an additional 45.7% reduction in the amount of time healthcare workers would spend with each patient. These results were presented as part of the European Lung Cancer Congress (ELCC) 2025 currently taking place in Paris. MSD’s senior vice president and head of oncology Marjorie Green said: “If approved, we are excited about the potential of SC Keytruda to become a new meaningful treatment option that may increase access and save time needed for administration compared to IV Keytruda. “We look forward to working with global regulatory authorities to bring the first SC checkpoint inhibitor that can be administered in approximately two minutes to patients and providers.” MSD’s Phase III 3475A-D77 recruited 377 patients from 110 locations internationally, splitting them into two arms. Among patients who received SC Keytruda with chemotherapy Grade III or above adverse events (AEs) occurred in 47% of patients versus 47.6% of patients who received IV Keytruda with chemotherapy. Within the past few years, several companies and therapies have made the shift towards SC formulations , in large part due to their ease of use, design and production over intravenous methods. Whilst IV Keytruda is present across a myriad of oncology indications, from kidney cancer to oesophageal cancer, GlobalData’s Pharmaceutical Intelligence Center estimates that the drug’s consistent growth in revenue won’t last forever as generic versions of the drug become available. By the end of 2029, Keytruda’s yearly sales are expected to peak at $15.6bn before steadily dropping down to $13bn by 2030, then further to $9.8bn by the end of 2031. GlobalData is the parent company of Clinical Trials Arena . Elsewhere in the field of therapies utilising MSD’s Keytruda, Mural Oncology is discontinuing the development of nemvaleukin alfa in ovarian cancer after a Phase III trial failed to improve overall survival (OS).

2025年3月25日，Mural Oncology plc（纳斯达克代码：MURA）宣布，由于其ARTISTRY-7 III期临床试验未能达到预期效果，将停止开发用于铂耐药卵巢癌（PROC）的Nemvaleukin Alfa。 受此消息影响，该公司股价大跌61%。 nemvaleukin，一种新的研究性IL-2变体，以扩大高剂量rhIL-2的治疗益处，同时减轻毒性。Nemvaleukin旨在避免结合Tregs和VECs，同时激活CD8 T细胞和NK细胞。（如下图所示） 在ARTISTRY-7试验中，Nemvaleukin Alfa与默沙东的抗PD-1疗法KEYTRUDA（帕博利珠单抗）联合使用，未能在统计学上显著改善患者的总生存期（OS）。试验结果显示，联合治疗组的中位总生存期为10.1个月，而化疗组为9.8个月，风险比（HR）为0.98。这意味着联合治疗并未比化疗提供显著的生存优势。 Mural Oncology表示，基于独立数据监测委员会的中期分析结果，公司认为该试验在最终分析中取得成功的可能性极低，因此决定停止该试验并终止Nemvaleukin Alfa在铂耐药卵巢癌中的开发。尽管如此，公司仍将继续推进其他临床项目，包括在黏膜黑色素瘤中的ARTISTRY-6试验，预计将在2025年第二季度公布该试验的初步结果。 尽管疗效未达预期，但Nemvaleukin Alfa在安全性方面表现出色。在超过800名患者中，Nemvaleukin Alfa无论是单独使用还是与帕博利珠单抗联合使用，均显示出良好的耐受性，与之前报告的数据一致。 Nemvaleukin目前仍正在一项潜在的注册性2期试验ARTISTRY-6中进行评估，该试验针对粘膜黑色素瘤（队列2），预计将于2025年第二季度公布数据。ARTISTRY-6队列3（单药治疗）和ARTISTRY-6队列4（联合治疗）的初步数据预计将在2025年第二季度公布，具体时间取决于患者入组情况。 结束语：此次试验失败对Mural Oncology来说是一个重大挫折，尤其是在铂耐药卵巢癌这一治疗选择有限的领域。铂耐药卵巢癌是一种难以治疗的肿瘤类型，患者通常对传统化疗药物产生耐药性，因此急需新的有效疗法。 识别微信二维码，可添加药时空小编 请注明：姓名+研究方向！