Johnson & Johnson (NYSE: JNJ) announced today new results from the Phase 2 RedirecTT-1 study evaluating the investigational combination of TALVEY® (talquetamab-tgvs), the first U.S. Food and Drug Administration (FDA)-approved GPRC5D-directed bispecific antibody, and TECVAYLI® (teclistamab-cqyv), the first FDA-approved BCMA-directed bispecific antibody. The results show a high overall response rate (ORR) with durability in patients with triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM) who have true extramedullary disease (EMD). EMD is defined as soft tissue/organ-associated plasmacytomas with no contact to bony structures as per International Myeloma Working Group (IMWG) criteria.1 RedirecTT-1 is the largest study dedicated to patients with EMD to date. These data were featured in a late-breaking oral presentation (Abstract #LB4001) at the 2025 European Hematology Association (EHA) Congress.

强生公司 (NYSE: JNJ) 今天公布了 II 期 RedirecTT-1 研究的新结果，该研究评估了 美国食品药品监督管理局 (FDA) 批准的首个针对 GPRC5D 的双特异性抗体 TALVEY® (talquetamab-tgvs) 与 FDA 批准的首个针对 BCMA 的双特异性抗体 TECVAYLI® ( teclistamab -cqyv) 的试验组合。结果显示，对于患有真正髓外疾病 (EMD) 的三级暴露 (TCE) 复发/难治性多发性骨髓瘤 (RRMM) 患者，总体缓解率 (ORR) 较高且持久。根据国际骨髓瘤工作组 (IMWG) 标准，EMD 定义为与骨结构无接触的软组织/器官相关浆细胞瘤。1 RedirecTT- 1是迄今为止针对 EMD 患者的最大规模研究。这些数据在2025 年欧洲血液学协会 (EHA) 大会的最新口头报告 (摘要编号#LB4001 ) 中进行了介绍。

EMD represents an aggressive form of multiple myeloma and occurs when myeloma cells spread and form tumors (plasmacytomas) elsewhere in the body, such as in soft tissues and organs. These patients often face limited treatment options and worse outcomes due to the complexity of the disease, including tumor heterogeneity, resulting in low ORRs and rapid relapses with current standard therapies. On average, TCE RRMM patients with EMD have an ORR of less than 40 percent and a median progression-free survival (PFS) of less than 6 months.

EMD 是多发性骨髓瘤的一种侵袭性类型，是指骨髓瘤细胞扩散至身体其他部位（例如软组织和器官）并形成肿瘤（浆细胞瘤）。由于疾病的复杂性（包括肿瘤异质性），这类患者通常面临有限的治疗选择和更差的预后，导致目前的标准疗法 ORR 较低且复发迅速。平均而言，伴有 EMD 的 TCE RRMM 患者的 ORR 低于 40%，中位无进展生存期 (PFS) 低于 6 个月。

"The investigational combination of TALVEY and TECVAYLI has demonstrated deep, durable responses in patients with relapsed or refractory multiple myeloma, and now shows great promise in those with extramedullary myeloma, where standard therapies often fall short," said Yael Cohen, M.D., Head of Myeloma Unit, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel.* "Dual targeting of GPRC5D and BCMA may lead to a higher ORR and greater depth of response by mitigating target antigen-related escape. The RedirecTT-1 trial shows the power of this novel dual-targeting combination approach as a potential treatment option for patients with this disease."

以色列特拉维夫索拉斯基医疗中心骨髓瘤科主任、医学博士 Yael Cohen 表示：“TALVEY 和 TECVAYLI 的试验性组合疗法已证明对复发或难治性多发性骨髓瘤患者具有深度、持久的缓解，目前也显示出对髓外骨髓瘤患者的巨大潜力，因为标准疗法往往无法达到疗效。”*“GPRC5D 和 BCMA 的双重靶向治疗可通过缓解靶抗原相关的逃逸来提高客观缓解率 (ORR) 并增强缓解深度。RedirecTT-1 试验证明了这种新型双重靶向组合疗法作为此类疾病患者潜在治疗选择的强大功效。”

The Phase 2 RedirecTT-1 study enrolled 90 patients with TCE RRMM with true EMD. Of these patients, 84.4 percent were triple-class refractory, 35.6 percent were penta-drug refractory, 20 percent had previously received BCMA CAR-T therapy, and 8.9 percent had previously received a bispecific antibody.3 The investigational combination of TALVEY® plus TECVAYLI® led to a high ORR of 78.9 percent (95 percent confidence interval [CI]; 69.0–86.8), with more than half of patients (54.4 percent) achieving complete response or better.3 High responses were observed even in patients exposed to prior BCMA CAR-T or anti-FcRH5 bispecific antibodies (83.3 percent ORR; 58.6-96.4 and 75 percent ORR; 34.9-96.8, respectively).3 Among responders, 66.2 percent remained in response at the data cutoff, with a median follow-up of 13.4 months, signaling deep and durable responses.3 Treatment with the combination resulted in 61 percent of patients progression free and alive at one year.3 Additionally, the combination led to durable responses, with 64.1 percent of patients maintaining response (median duration of response: 13.8 months) and 74.5 percent of patients alive at one year, while median overall survival was not yet reached.

2 期 RedirecTT-1 研究入组了 90 名患有 TCE RRMM 且伴有真性 EMD 的患者。其中，84.4% 为三药难治，35.6% 为五药难治，20% 曾接受过 BCMA CAR-T 疗法，8.9% 曾接受过双特异性抗体治疗。3 TALVEY®联合TECVAYLI®疗法 的试验性组合疗法取得了高达 78.9% 的客观缓解率 (ORR)（95% 置信区间 [CI]：69.0-86.8），超过一半的患者（54.4%）达到完全缓解或更佳疗效。3即使在接受过 BCMA CAR-T 疗法或抗 FcRH5 双特异性抗体治疗的患者中，也观察到了较高的缓解率（分别为 83.3% 的 ORR；58.6-96.4% 和 75%的 ORR；34.9-96.8%）。3 在应答者中，66.2% 的患者在数据截止时仍保持应答，中位随访时间为 13.4 个月，这表明应答深度持久。3 联合治疗使 61% 的患者病情无进展并在一年内存活。3此外，联合治疗还带来了持久的应答，64.1% 的患者维持应答（中位 应答持续时间：13.8 个月），74.5% 的患者在一年内存活，但中位总生存期尚未达到。

"Patients with extramedullary myeloma, especially those who have exhausted prior therapies, need more effective treatment options," said Jordan Schecter, M.D., Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. "Our first-in-class bispecific antibodies TALVEY and TECVAYLI have transformed treatment for relapsed or refractory multiple myeloma. The RedirecTT-1 study underscores our commitment to advancing innovative therapies that attack the disease in different ways by building combinable and complementary regimens."

强生创新医学副总裁兼多发性骨髓瘤疾病领域负责人Jordan Schecter医学博士表示：“髓外骨髓瘤患者，尤其是那些既往疗法已失效的患者，需要更有效的治疗方案。我们首创的双特异性抗体TALVEY和TECVAYLI已经彻底改变了复发或难治性多发性骨髓瘤的治疗方案。RedirecTT-1研究彰显了我们致力于推进创新疗法的承诺，通过构建可组合和互补的方案，以不同的方式对抗这种疾病。”

The safety profile of the combination was consistent with previous reports of TALVEY® and TECVAYLI® as monotherapies, with no new safety signals identified.3 Patients were given the option to switch to once a month dosing, potentially contributing to improved tolerability. Rates of discontinuation were low with the treatment combination of TALVEY® and TECVAYLI® due to adverse events (AEs).3 Four participants discontinued TALVEY® only.3 Reports of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were mostly low grade.3 Of the ten patients who had Grade 5 AEs (11.1 percent), five were due to infections and five were unrelated.3 The rates of severe infection were similar to those observed with BCMA bispecific antibody monotherapies.

该组合的安全性与之前 TALVEY ®和 TECVAYLI ®单药治疗的报告一致，未发现新的安全信号。3患者可以选择改为每月一次给药，这可能有助于提高耐受性。TALVEY ®和 TECVAYLI ®组合治疗的停药率较低，原因是不良事件 (AE)。3四名参与者仅停用了 TALVEY ®。3 CRS 和免疫效应细胞相关神经毒性综合征 (ICANS) 的报告大多为低级别。3在10名出现 5 级 AE 的患者（11.1%）中，5 名是由于感染，5 名与此无关。3严重感染的发生率与 BCMA 双特异性抗体单药治疗的 发生率相似。