Talquetamab

2025年6月15日,强生公司公布了II期RedirecTT-1研究的最新数据，这是一项评估全球首个GPRC5D靶向双抗TALVEY®（talquetamab-tgvs）与首个BCMA靶向双抗TECVAYLI®（teclistamab-cqyv）的联合疗法的临床试验。结果显示，在三重暴露（TCE）复发/难治性多发性骨髓瘤（RRMM）伴真实髓外病变（EMD）患者中，该组合疗法实现高客观缓解率（ORR）与持久缓解。EMD根据国际骨髓瘤工作组（IMWG）标准定义为与骨结构无关联的软组织/器官浆细胞瘤。RedirecTT-1是迄今规模最大的EMD患者专属研究，数据以重磅口头报告（摘要#LB4001）形式亮相2025年欧洲血液学协会（EHA）年会。EMD是多发性骨髓瘤的侵袭性亚型，表现为骨髓瘤细胞扩散至软组织及器官形成浆细胞瘤。由于肿瘤异质性等因素，这类患者现有标准疗法的ORR通常低于40%，中位无进展生存期（PFS）不足6个月。"TALVEY与TECVAYLI联合疗法已在RRMM患者中展现深度持久缓解，现对标准疗法疗效有限的髓外骨髓瘤同样显示出潜力，"以色列特拉维夫Sourasky医学中心骨髓瘤科主任Yael Cohen博士表示，"同时靶向GPRC5D和BCMA可能通过减少抗原逃逸实现更高ORR和更深缓解。RedirecTT-1研究验证了这一创新双靶点策略的价值。"该研究纳入了90例TCE RRMM伴真实EMD患者，其中84.4%为三重难治性，35.6%为五药难治性，20%曾接受BCMA CAR-T治疗，8.9%曾接受双抗治疗。联合疗法ORR达78.9%（95%CI: 69.0-86.8），54.4%患者达到完全缓解或更好。既往接受BCMA CAR-T或抗FcRH5双抗治疗患者的ORR分别为83.3%和75%。截至数据截止时（中位随访13.4个月），66.2%缓解者仍持续缓解，61%患者在一年时无进展生存，74.5%患者存活（中位总生存期未达到）。强生创新医学多发性骨髓瘤领域副总裁Jordan Schecter博士指出："对于经治EMD患者，我们首创的双抗TALVEY和TECVAYLI通过构建可组合的互补方案，展现了攻克这一疾病的创新路径。"联合疗法的安全性与单药治疗一致，未发现新安全信号。患者可转换为每月给药方案以改善耐受性，因不良事件（AE）导致的治疗中止率较低。10例患者报告5级AE（11.1%），其中5例与感染相关。严重感染发生率与BCMA双抗单药治疗相当。信息来源:https://www.jnj.com/media-center/press-releases/investigational-combination-of-first-in-class-bispecifics-talvey-and-tecvayli-shows-deep-and-durable-responses-in-heavily-pretreated-multiple-myeloma-patients-with-extramedullary-disease药事纵横投稿须知：稿费已上调，欢迎投稿

Johnson & Johnson's investigational combination of Talvey (talquetamab) and Tecvayli (teclistamab) showed deep and sustained responses in a mid-stage study of patients with extramedullary triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM). The data were presented as a late-breaker at the European Hematology Association (EHA) congress on the weekend.While Talvey is a bispecific antibody targeting GPRC5D and CD-3, Tecvayli is a BCMA and CD3-directed bispecific. According to the company, the combination targets GPRC5D and BCMA in extramedullary disease — potentially overcoming treatment resistance mechanisms. “The…study reflects our strategy to harness…the combination of these dual bispecific antibodies, to help redefine potential outcomes for subsets of patients who are currently faced with a poor prognosis and limited options,” said Ester in't Groen, EMEA therapeutic area head for haematology at Johnson & Johnson Innovative Medicine. Data from the Phase Ib portion of the RedirecTT-1 study unveiled last year showed Talvey plus Tecvayli achieved a 79.5% overall response rate (ORR) and a 52.3% complete response or better (CR+) rate in patients with TCE RRMM; corresponding rates in the extramedullary disease subgroup were 61.1% and 33.3%.The Phase II part enrolled 90 patients with TCE RRMM presenting with true extramedullary disease, defined as soft tissue plasmacytomas without bone contact. Patient characteristics reflected heavily pretreated populations: 84.4% were triple-class refractory, 35.6% penta-drug refractory, and 20% had received prior BCMA CAR-T therapy.Results showed the combination of Talvey and Tecvayli demonstrated a 78.9% ORR, with 54.4% of patients achieving CR+. Durability metrics showed 66.2% of responders maintained response at median 13.4-month follow-up, whilst progression-free survival reached 61% at one year. Moreover, 64.1% of patients maintained response for a median of 13.8 months and 74.5% were alive at one year; median overall survival was not reached.Additionally, the combination maintained robust efficacy across subgroups, including patients with prior BCMA CAR-T exposure (83.3% response rate) and anti-FcRH5 bispecific antibody treatment (75% response rate). Meanwhile, adverse event profiles remained consistent with established monotherapy safety data, with no new safety signals identified. Grade 5 adverse events occurred in 11.1% of patients, with infections representing the primary fatal complication in five cases. Cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome presentations were predominantly low-grade.Both bispecifics are individually approved in the EU and US for adults with RRMM, who have previously received three and four lines of therapy, respectively.