Mosunetuzumab

Updated data from the pivotal phase III STARGLO study continue to demonstrate a clinically meaningful improvement in overall survival with a 40% survival benefit for people with R/R DLBCL who are not candidates for transplant1 89% of patients whose cancer had fully responded at the end of treatment with Columvi in combination with chemotherapy were still alive and 82% showed no signs of cancer one year post-treatment1 Timely initiation of effective therapy at relapse or after initial therapy failure is critical for this aggressive, life-threatening disease Results demonstrate potential of the Columvi combination as a much-needed, off-the-shelf and fixed-duration treatment option Basel, 23 May 2025 - Roche (SIX: RO, ROG; OTCQX: RHHBY) announced today two-year follow-up data from the phase III STARGLO study. After a median follow-up of 24.7 months, data showed a 40% improvement in overall survival (OS) for patients treated with Columvi® (glofitamab) in combination with gemcitabine and oxaliplatin (GemOx) and OS was not reached, compared to 13.5 months for MabThera®/Rituxan® (rituximab) plus GemOx (R-GemOx).1 These updated data continue to demonstrate the statistically significant and clinically meaningful survival benefit of this off-the-shelf, fixed-duration Columvi combination for people with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) who have received at least one prior line of therapy and are not candidates for autologous stem cell transplant (ASCT).1 Data will be presented in an oral session at the 61st American Society of Clinical Oncology (ASCO), 30 May – 3 June 2025. “We are encouraged that the two-year follow-up data for Columvi reinforces its potential to extend the lives of many patients where prognosis has historically been poor,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “These findings demonstrate the potential lasting benefits of early and effective treatment initiation with a bispecific antibody for people with relapsed or refractory disease.” "When cancer comes back or doesn’t respond to treatment, it’s devastating for patients with DLBCL given the aggressive nature of the disease,” said Haifaa Abdulhaq, MD, Professor, University of California San Francisco (UCSF), Director of Hematology, UCSF Fresno. “In my community practice, I’ve seen the potential of this Columvi combination to help patients start treatment quickly - providing lasting remissions and more time without ongoing therapy.” The benefit across key secondary endpoints, including progression-free survival (PFS) and complete remission (CR), was maintained for patients treated with the Columvi combination.1 There was a 59% reduction in the risk of disease progression or death (hazard ratio = 0.41, 95% confidence interval: 0.29–0.58) and more than twice as many patients sustained a CR (58.5% vs. 25.3%).1 Among patients with a CR at the end of the treatment period, 89% were alive and 82% had maintained remission one year after treatment.1 Safety of the combination remained unchanged from the previous analysis and was consistent with the known safety profiles of the individual medicines.1,2 Patients received a higher median number of cycles of the Columvi combination (11 versus 4), due to disease progression in the R-GemOx arm.1,2 A higher rate of adverse events (AEs) was observed with the Columvi regimen. One of the most common AEs was cytokine release syndrome, which was generally low grade.1 Given the wide adoption of global treatment guidelines in real-world clinical practice, there are no biological or clinical differences in DLBCL management worldwide.3-6 While second-line therapies have advanced, DLBCL can progress rapidly and many people are not candidates for, cannot tolerate, or do not have access to latest therapies.7,8 There is an urgent need for treatments that are rapidly available upon a diagnosis of relapse, that can manage the disease and improve long-term outcomes. Based on the STARGLO data, this Columvi combination is approved in more than 30 countries for people with R/R DLBCL who are not candidates for ASCT, including countries throughout the EU. Columvi in combination with GemOx was added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) as an NCCN category 1 preferred recommendation for the treatment of people with second-line DLBCL who are not intended to proceed to transplant.†3 Columvi monotherapy has been approved for use in R/R DLBCL after two or more prior lines of therapy in more than 60 countries worldwide. Columvi is part of Roche’s industry-leading CD20xCD3 bispecific antibody programme. Together with the clinical development of off-the-shelf allogeneic CAR T-therapies, Roche aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems. The STARGLO study [GO41944; NCT04408638] is a phase III, multicentre, open-label, randomised study evaluating the efficacy and safety of Columvi® (glofitamab) in combination with gemcitabine plus oxaliplatin (GemOx) versus MabThera®/Rituxan® (rituximab) in combination with GemOx in patients with relapsed or refractory diffuse large B-cell lymphoma who have received at least one prior line of therapy and who are not candidates for autologous stem cell transplant, or who have received two or more prior lines of therapy. Preclinical research indicated an increased antitumour effect when combining Columvi with GemOx over GemOx alone, so the STARGLO study was initiated to further explore the potential complementary effects of the treatment combination. Outcome measures include overall survival (primary endpoint), progression-free survival, complete response rate, objective response rate, duration of objective response (secondary endpoints), and safety and tolerability. Columvi is a CD20xCD3 T-cell engaging bispecific antibody designed to target CD3 on the surface of T cells and CD20 on the surface of B cells. Columvi was designed with a novel 2:1 structural format. This T-cell engaging bispecific antibody is engineered to have one region that binds to CD3, a protein on T cells, a type of immune cell, and two regions that bind to CD20, a protein on B cells, which can be healthy or malignant. This dual-targeting brings the T cell in close proximity to the B cell, activating the release of cancer cell-killing proteins from the T cell. Columvi is part of Roche’s broad and industry-leading CD20xCD3 T-cell-engaging bispecific antibody clinical development programme that also includes Lunsumio® (mosunetuzumab), which aims to provide tailored treatment options that suit the diverse needs, preferences, and experiences of people with blood cancers and healthcare systems. Roche is investigating Columvi as a monotherapy and in combination with other medicines for the treatment of diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma. As part of Roche’s efforts to elevate treatment standards in the earlier stages of DLBCL, where there is the best opportunity to improve long-term outcomes and prevent relapse, Columvi is also being investigated in combination with Polivy® (polatuzumab vedotin) and MabThera®/Rituxan® (rituximab), cyclophosphamide, doxorubicin and prednisone (R-CHP) in previously untreated DLBCL in the phase III SKYGLO study [GO44145; NCT06047080]. DLBCL is an aggressive (fast-growing) type of non-Hodgkin lymphoma (NHL) and the most common form, accounting for about one in three cases of NHL.9 Approximately 160,000 people worldwide are diagnosed with DLBCL each year, with comparable incidence rates across regions.9,10 Medical practices, including pathological classification, diagnosis, staging, initial treatment and relapse management, are similarly approached worldwide.3-6 While it is generally responsive to treatment in the frontline, as many as 40% of people will relapse or have refractory disease, at which time salvage therapy options are limited and survival is short.7,11 Improving treatments earlier in the course of the disease and providing much needed alternative options could help to improve long-term outcomes. Roche has been developing medicines for people with malignant and non-malignant blood diseases for more than 25 years; our experience and knowledge in this therapeutic area runs deep. Today, we are investing more than ever in our effort to bring innovative treatment options to patients across a wide range of haematologic diseases. Our approved medicines include MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), Polivy® (polatuzumab vedotin), Venclexta®/Venclyxto® (venetoclax) in collaboration with AbbVie, Hemlibra® (emicizumab), PiaSky® (crovalimab), Lunsumio® (mosunetuzumab) and Columvi® (glofitamab). Our pipeline of investigational haematology medicines includes T-cell engaging bispecific antibody cevostamab, targeting both FcRH5 and CD3 and Tecentriq® (atezolizumab). Our scientific expertise, combined with the breadth of our portfolio and pipeline, also provides a unique opportunity to develop combination regimens that aim to improve the lives of patients even further. Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. For over 125 years, sustainability has been an integral part of Roche’s business. As a science-driven company, our greatest contribution to society is developing innovative medicines and diagnostics that help people live healthier lives. Roche is committed to the Science Based Targets initiative and the Sustainable Markets Initiative to achieve net zero by 2045. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. †NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. References [1] Abramson J, et al. Glofitamab plus gemcitabine and oxaliplatin (Glofit-GemOx) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): 2-year (yr) follow-up of STARGLO. Presented at: ASCO Annual Meeting; 2025 May 30 - Jun 3. Abstract #7015. [2] Abramson J, et al. Glofitamab plus gemcitabine and oxaliplatin (GemOx) versus rituximab-GemOx for relapsed or refractory diffuse large B-cell lymphoma (STARGLO): a global phase 3, randomised, open-label trial. Lancet 2024; 404 (10466): 1940-1954. [3] NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.1.2025. [4] Tilly H, et al. Diffuse large B-cell lymphoma (DLBCL): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26:v116-25. [5] Zhu J, et al. Union for China Lymphoma Investigators of Chinese Society of Clinical Oncology. Chinese Society of Clinical Oncology (CSCO) diagnosis and treatment guidelines for malignant lymphoma 2021 (English version). Chin J Cancer Res. 2021;30;33(3):289-301. [6] Wight J, et al. Diffuse large B-cell lymphoma: a consensus practice statement from the Australasian Lymphoma Alliance. Intern Med J. 2022;52(9):1609-1623. [7] Fabbri N, et al. Second-line treatment of diffuse large B-cell lymphoma: Evolution of options. Semin Hematol 2023; 60(5): 305–312. [8] Westin J, et al. CAR T cells as a second-line therapy for large B-cell lymphoma: A paradigm shift? Blood. 2022;139(18):2737–2746. [9] UpToDate. Patient education: Diffuse large B cell lymphoma in adults (Beyond the Basics). [Internet; cited May 2025]. Available from: https://www-uptodate-com.libproxy1.nus.edu.sg/contents/diffuse-large-b-cell-lymphoma-in-adults-beyond-thebasics. [10] World Health Organization. Numbers derived from GLOBOCAN 2022. Non-Hodgkin Lymphoma Factsheet [Internet; cited May 2025]. Available from: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/cancers/34-nonhodgkin-lymphoma-fact-sheet.pdf. [11] Sehn LH, et al. Diffuse Large B-Cell Lymphoma. N Engl J Med. 2021;384(9):842-858. The content above comes from the network. if any infringement, please contact us to modify.

PD-(L)1药物问世已有11年，Keytruda（帕博利珠单抗）的销售峰值也逼近300亿美元并仍在刷新纪录，超越了前一代“药王”Humira（阿达木单抗）创下的最高纪录。这是抗肿瘤药物第一次登上如此高峰，也是肿瘤免疫治疗1.0时代的市场胜利。而今，肿瘤治疗的创新潮流已汹涌奔向新的方向：抗体偶联药物（ADC）和T细胞衔接器（TCE）正引领下一代革命。ADC和TCE成为肿瘤治疗风口的逻辑清晰：前者可精准高效杀伤肿瘤细胞，具备替代传统化疗的潜力；后者可募集T细胞“大军”，是强化细胞免疫应答的关键武器。站上这两个风口，也就有可能成为下一个肿瘤治疗格局变革者。中国药企正在抓住这一机会，迈威生物就是其中的生力军。2024年，迈威生物的9MW2821（Nectin-4 ADC）入选美国临床肿瘤学会（ASCO）年会口头报告，首次亮相即崭露头角；2025年，迈威生物又在美国癌症研究协会（AACR）年会上展示其新型payload和TCE技术平台的最新进展。这些成果映射出迈威生物清晰的战略布局——通过ADC和TCE双平台驱动，在肿瘤治疗领域逐步构建差异化竞争优势，逐步完成从行业“新星”到创新药“高阶玩家”的跃级。ADC布局：锚定蓝海区迈威生物进军ADC的时间较早，当时这一概念还未在国内被炒热，不过部分靶点已隐隐有扎堆之势。考虑到这一点，迈威生物采取了明智的差异化策略——构建特色平台，避开HER2等靶点“红海区”，押注Nectin-4、B7-H3、CDH17等潜力靶点，以差异化管线破局。9MW2821（Bulumtatug fuvedotin）作为迈威生物ADC管线的领军产品，是首个启动临床的国产Nectin-4 ADC，正试图打破Padcev（维恩妥尤单抗）一枝独秀的局面。在尿路上皮癌（UC）这一核心战场上，9MW2821与先行者Padcev展开了实力角逐，已经在临床数据上展示出best in class（BIC）潜力。对于接受过一线治疗的UC患者，9MW2821的客观缓解率（ORR）达到了54.1%[1]，这一数据已超越Padcev的表现（37.5%）[2]。而在一线治疗UC的探索中，9MW2821联合特瑞普利单抗将患者的ORR提高至87.5%，确认的ORR也高达80.0%[3]，再次彰显其BIC潜力。这一突出表现为9MW2821争取到了CDE授予的第二项突破性疗法资格，用于联合特瑞普利单抗治疗既往未经系统治疗的、不可手术切除的局部晚期或转移性UC。9MW2821和维恩妥尤单抗的一线UC临床数据“ADC+PD-1”的联用模式正在成为肿瘤治疗的重要趋势，Padcev（维恩妥尤单抗）+Keytruda（帕博利珠单抗）已获FDA批准用于一线治疗UC。9MW2821与特瑞普利单抗的组合展现出了类似甚至更好的疗效，为中国乃至全球患者带来新的治疗希望。9MW2821的差异化优势在三阴性乳腺癌（TNBC）适应症上更加明显。I/II期研究数据显示，拓扑异构酶抑制剂（TOPi）经治TNBC患者接受治疗后，ORR达到50.0%，与Padcev（维恩妥尤单抗）拉开较大差距[4]。TNBC是乳腺癌预后最差的亚型，治疗选择有限，现有一线治疗药物仅有PD-(L)1药物，后线治疗药物（TROP2 ADC）的ORR为35.0%-45.4%[5-8]，患者获益亟待提高。考虑到目前获批和临床研究后期的ADC药物多使用TOPi为载荷，以MMAE为载荷的9MW2821有望为TOPi ADC经治TNBC患者的后续治疗提供保障。此外，9MW2821也在开展联合PD-1药物治疗TNBC的II期临床，有望为TNBC患者提供更有效的前线治疗选择。在其它新兴靶点上的布局，迈威生物也有所收获。7MW3711（B7-H3 ADC）在临床前研究中展现出了与PARP抑制剂联用的协同抗肿瘤活性，为前列腺癌治疗提供了新思路。此外，7MW3711联合PD-1药物的临床试验申请已在今年4月获批，这一组合也是同类产品的热门验证方向。在即将举行的ASCO 2025大会上，迈威生物将公布7MW3711的单药数据，这将是进一步验证该分子潜力的重要窗口。7MW4911则聚焦胃肠道肿瘤高表达的靶点——CDH17。目前，全球临床阶段CDH17 ADC项目仍相对稀少，主要玩家包括普众发现、翰森制药、宜联生物等。迈威生物的7MW4911虽然仍处于临床前阶段，但其采用的创新载荷——非P-糖蛋白（P-gp）底物的MF-6，有望克服胃肠道肿瘤常见的多药耐药问题，带来显著的临床优势。在ADC药物设计中，载荷的选择直接影响药物的疗效和安全性。MF-6是迈威生物通过其专有的Mtoxin平台开发的一种载荷，已应用于三款在研ADC产品——7MW3711、7MW4911和9MW2921，显示出广泛的应用前景。与此同时，迈威生物还与英矽智能合作，利用AI技术开发新型毒素，进一步强化技术壁垒。从传统双抗到TCE，迈威生物玩法升级随着免疫治疗的深入发展，TCE技术的应用已从血液瘤扩展至实体瘤，成为继ADC之后肿瘤治疗的下一个热点。在这一技术变革中，迈威生物的布局同样展现出前瞻性的战略视野。最初，迈威生物在传统双抗领域试水，积累开发经验后进入TCE赛道。在今年1月份披露的港交所招股书中，迈威生物首次透露了TCE双/三特异性抗体平台的建成。紧接着，该平台便在AACR 2025年会上正式亮相。这一平台的核心在于其精准的工程学设计，能够兼顾CD3亲和力、TCE format、肿瘤相关抗原（TAA）筛选及细胞因子释放综合征（CRS）风险等复杂因素。为实现这一目标，迈威生物开发了一组具有不同结合特征和活化特性的经改造靶向CD3抗体，以及针对T细胞激活的二级信号的激动型抗体。同时，迈威生物建立了多组学的靶点筛选及评估体系，以鉴定肿瘤相关抗原（TAA）并确定其优先级。基于这些技术创新，迈威生物开发了高效且安全的1+1、1+2、2+2等多种TCE format，以适应不同肿瘤类型的治疗需求。基于该平台设计的TCE分子能够精准控制T细胞激活的强度和持续时间，并且诱发CRS的风险也更低[9]。此外，它们可与食蟹猴CD3发生交叉反应，便于在非人灵长类动物模型中评估TCE介导的细胞毒性。与TCE平台同时亮相的还有基于该平台研发的首个临床前项目——2MW7061。这是一款设计巧妙的1+2 TCE双抗，其结构包含两个靶向白细胞免疫球蛋白样受体B4（LILRB4）的Fab片段和一个靶向CD3的单链可变（scFv）片段，可通过空间位阻效应实现靶向依赖性T细胞激活。在临床前模型中，2MW7061对LILRB4低表达和高表达肿瘤均显示出了显著的抑制生长作用[10]，并在非人灵长类动物中表现出良好的安全性，为后续临床开发奠定了基础。在肿瘤治疗的组合玩法趋势下，TCE亦存在联用的可能性。“TCE+ADC”或“TCE+IO”的组合已在全球范围内开展临床探索，初步数据显示出令人鼓舞的抗肿瘤活性。以罗氏的研究为例，在一项II期研究中，大B细胞淋巴瘤（LBCL）患者接受莫妥珠单抗联用维泊妥珠单抗治疗后，ORR达到了78%，并且有58%的患者实现了完全缓解（CR）[11]。这种联合治疗趋势，为拥有ADC和TCE双平台的迈威生物提供了广阔的战略空间。“TCE+ADC/IO”组合临床试验开展情况来源：医药魔方TrialCube数据库总结无论是单药开发还是联合治疗，ADC与TCE均具备广阔的市场空间。从目前来看，迈威生物凭借其前瞻性布局，以双技术平台为引擎，不仅构建了差异化的产品矩阵，更通过突破性临床数据展示了中国创新药企的全球竞争力，但竞争之下仍需加速临床转化并证明联合治疗策略的临床价值，方能在巨头林立的行业中稳固地位。无论如何，从国际学术舞台上的频繁亮相，到多元化的技术平台和产品管线，迈威生物正一步步从肿瘤治疗领域的“新星”，成长为具有独特竞争力的“高玩”。在中国创新药企不断崛起的大背景下，这家企业正下一盘长远的战略棋局，其未来发展值得期待。- 上下滑动查看参考资料 - [1] 9MW2821, a next-generation Nectin-4 targeting antibody-drug conjugate, in patients with advanced solid tumors: a first-in-human, open label, multicenter, phase I/II study. Annals of Oncology. 2025; S0923-7534(25)00169-3.[2] Enfortumab Vedotin Plus Pembrolizumab in Previously Untreated Advanced Urothelial Cancer. Journal of Clinical Oncology. 2023; 41(1):22-31.[3] ORR 87.5%，迈威生物靶向 Nectin-4 ADC 创新药 9MW2821联合治疗一线被纳入 CDE 突破性治疗品种名单. 迈威生物公众号.[4] Enfortumab vedotin (EV) in triple-negative breast cancer (TNBC) and HR+/HER2- breast cancer (BC) cohorts of EV-202. Journal of Clinical Oncology. 2024; 42(16_suppl).[5] Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. New England Journal of Medicine. 2025; 384(16):1529-1541.[6] 248P Sacituzumab govitecan in Chinese patients with metastatic triple-negative breast cancer who received at least two prior treatments. ESMO 2022.[7] Sacituzumab tirumotecan in previously treated metastatic triple-negative breast cancer: a randomized phase 3 trial. Nature Medicine. 2025.[8] 2023 SABCS|科伦博泰生物公布SKB264(MK-2870)治疗三阴性乳腺癌最新临床研究结果. 科伦博泰生物公众号.[9] Abstract 2866: An innovative T cell engager platform with optimized CD3 affinity and formats for targeting hematologic and solid tumors. Cancer Research. 2025; 85 (8_Supplement_1): 2866.[10] Abstract 2116: 2MW7061, a novel LILRB4xCD3 bispecific T-cell engager targeting monocytic acute myeloid leukemia. Cancer Research. 2025; 85 (8_Supplement_1): 2116.[11] A Randomized Phase II Study of Mosunetuzumab SC Plus Polatuzumab Vedotin Demonstrates Improved Outcomes Versus Rituximab Plus Polatuzumab Vedotin in Patients (Pts) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL). ASH 2024.Copyright © 2025 PHARMCUBE. All Rights Reserved.欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。