The FDA has accepted and granted priority review to a new drug application (NDA) for vimseltinib (DCC-3014), a colony-stimulating factor 1 receptor (CSF1R)-directed therapy, for the treatment of patients with tenosynovial giant cell tumor (TGCT), according to a press release from Ono Pharmaceutical, which added that the regulatory body assigned a Prescription Drug User Fee Act goal date of February 17, 2025.

根据Ono Pharmaceutical的新闻稿，FDA已接受并批准优先审查用于治疗腱鞘巨细胞瘤（TGCT）患者的vimseltinib（DCC-3014）新药申请（NDA），这是一种集落刺激因子1受体（CSF1R）导向的治疗方法，用于治疗腱鞘巨细胞瘤（TGCT）。该新闻稿补充说，监管机构指定了2025年2月17日的处方药用户费用法案目标日期。

The NDA is supported by data from the phase III MOTION study (NCT05059262) which evaluated treatment with vimseltinib vs placebo in patients with TGCT. At the 2024 ASCO Annual Meeting, investigators shared that at week 25, patients treated with vimseltinib (n = 83) achieved a statistically significant and clinically meaningful overall response rate (ORR) of 40% (95% CI, 29%-51%; P < .0001) compared with 0% in patients treated with placebo (n = 40)..

NDA得到了III期运动研究（NCT05059262）的数据支持，该研究评估了vimseltinib与安慰剂对TGCT患者的治疗效果。在2024年ASCO年会上，研究人员分享说，在第25周，接受vimseltinib治疗的患者（n=83）达到了40%的统计学显着性和临床意义的总体缓解率（ORR）（95%可信区间，29%-51%；P<0.0001），而安慰剂治疗的患者（n=40）为0%。。

“Building upon positive results from the MOTION pivotal phase III study and following our recent announcement that [the] European Medicines Agency [EMA] review of the vimseltinib’s marketing authorization application [MAA] has begun, we are excited to initiate the regulatory review process in the United States and we look forward to working with the FDA to deliver a new treatment option to patients with TGCT,” Steve Hoerter, president and chief executive officer of Deciphera Pharmaceuticals, stated in a news release..

Deciphera Pharmaceuticals总裁兼首席执行官史蒂夫·霍尔特（SteveHoerter）在新闻稿中表示：“基于MOTION pivotal III期研究的积极成果，以及我们最近宣布欧洲药品管理局（EMA）已经开始对vimseltinib的上市授权申请（MAA）进行审查，我们很高兴在美国启动监管审查程序，我们期待着与FDA合作，为TGCT患者提供新的治疗选择。”。。

The EMA accepted the MAA for vimseltinib in July 2024, beginning the EMA’s centralized review process of the agent. The regulatory submission and acceptance was also supported by data from the international, randomized, double-blind MOTION study.

EMA于2024年7月接受了vimseltinib的MAA，开始了EMA对该药物的集中审查过程。监管机构的提交和接受也得到了国际随机双盲运动研究数据的支持。

TGCT is a rare, non-malignant tumor that forms in or near joints due to overexpression of CSF1, leading to inflammation and tissue damage. Surgery is the primary treatment, but these tumors often recur, necessitating new therapeutic options. Vimseltinib is an investigational drug designed to selectively inhibit CSF1R; the agent is thereby being investigated in the 2-part, placebo-controlled MOTION trial..

TGCT是一种罕见的非恶性肿瘤，由于CSF1的过度表达而在关节内或附近形成，导致炎症和组织损伤。手术是主要的治疗方法，但这些肿瘤经常复发，需要新的治疗选择。Vimseltinib是一种研究药物，旨在选择性抑制CSF1R；因此，该药物正在由两部分组成的安慰剂对照运动试验中进行研究。。

The trial enrolled patients at least 18 years of age with a confirmed diagnosis of symptomatic TGCT not amenable to surgery and no prior anti-CSF1/CSF1R therapy. Eligible patients were randomly assigned 2:1 to receive 30 mg of vimseltinib twice weekly or placebo for 24 weeks. During the open-label period of the trial patients were eligible to continue treatment with vimseltinib or cross over to receive vimseltinib if they had been assigned to the placebo arm.

该试验招募了至少18岁的患者，确诊为症状性TGCT不适合手术，并且之前没有抗CSF1/CSF1R治疗。符合条件的患者被随机分配为2:1，每周两次接受30 mg vimseltinib或安慰剂治疗24周。。

The primary end point of the MOTION trial was ORR by independent radiological review (IRR) using RECIST 1.1 criteria at week 25; secondary end points included IRR-assessed ORR by tumor volume score (TVS), change from baseline in active range of motion, and patient-reported outcomes..

MOTION试验的主要终点是在第25周使用RECIST 1.1标准通过独立放射学评估（IRR）进行ORR；次要终点包括通过肿瘤体积评分（TVS）评估的IRR ORR，活动范围与基线的变化以及患者报告的结果。。

Additional results from the trial indicated that the agent demonstrated robust and statistically significant antitumor activity by TVS, with an ORR of 67% (95% CI, 56%-77%) vs 0% with placebo (P < .0001). The median duration of response (DOR) with vimseltinib using RECIST 1.1 criteria was not reached ([NR] range, 0.03+ to 11.7+ months) and the median DOR using TVS was also NR (range, 0.03+ to 13.9+ months)..

该试验的其他结果表明，该药物通过TVS显示出强大且具有统计学意义的抗肿瘤活性，ORR为67%（95%CI，56%〜77%），而安慰剂为0%（P<0.0001）。使用RECIST 1.1标准的vimseltinib的中位反应持续时间（DOR）未达到（[NR]范围，0.03+至11.7+个月），使用TVS的中位DOR也是NR（范围，0.03+至13.9+个月）。。

Vimseltinib also demonstrated statistically significant and clinically meaningful improvements vs placebo across all key secondary end points. From baseline the agent led to improvements in active range of motion (18.4% vs 3.8%; difference, 14.6%; P = .0077), as well as PROMIS-Physical Function (mean change, 4.6 vs 1.3; difference, 3.3; P = .0007).

Vimseltinib在所有关键次要终点与安慰剂相比也显示出统计学上显着和临床上有意义的改善。从基线开始，该药物导致活动范围的改善（18.4%比3.8%；差异14.6%；P=0.0077），以及PROMIS身体功能（平均变化4.6比1.3；差异3.3；P=0.0007）。

Additionally, vimseltinib led to improvements in worst stiffness Numeric Rating Scale (mean change, –2.1 vs –0.3; difference, –1.8; P < .0001), EQ-Visual Analogue Scale (mean change, 13.5 vs 6.1; difference, 7.4; P = .0155), and Brief Pain Inventory (40% vs 9%; difference, 26%; P = .0056)..

此外，vimseltinib导致最差刚度数字评定量表（平均变化，-2.1 vs-0.3；差异，-1.8；P<0.0001），EQ视觉模拟量表（平均变化13.5 vs 6.1；差异7.4；P=0.0155）和简短疼痛量表（40%比9%；差异26%；P=0.0056）的改善。。

Vimseltinib also demonstrated a manageable safety profile that was well tolerated. The most common treatment-emergent adverse effects (TEAEs) included periorbital edema (all grade, 45%; grade 3/4, 4%), fatigue (33%; 0%), face edema (31%; 1%), pruritus (29%; 2%), and headache (28%; 1%). Notably, there was no evidence of cholestatic hepatotoxicity, drug-associated liver injury, or hair/skin hypopigmentation.

Vimseltinib还表现出可控的安全性，耐受性良好。最常见的治疗紧急不良反应（TEAE）包括眶周水肿（所有级别，45%；3/4级，4%），疲劳（33%；0%），面部水肿（31%；1%），瘙痒（29%；2%）和头痛（28%；1%）。值得注意的是，没有证据表明胆汁淤积性肝毒性，药物相关性肝损伤或头发/皮肤色素沉着不足。

TEAEs resulted in treatment discontinuation in 6% of patients who received vimseltinib..

TEAE导致接受vimseltinib治疗的患者中有6%停止治疗。。

See- Tap WD, Bhadri V, Stacchiotti S, et al. 'Efficacy, safety, and patient-reported outcomes of vimseltinib in patients with ten osynovial giant cell tumor: results from the phase III MOTION trial'. J Clin Oncol. 2024;42(suppl 16):11500. doi:10.1200/JCO.2024.42.16_suppl.11500.

参见-Tap WD，Bhadri V，Stacchiotti S等，“vimseltinib在10例osynovial巨细胞瘤患者中的疗效，安全性和患者报告的结果：III期运动试验的结果”。J临床肿瘤学。2024年；42（补充16）：11500。doi:10.1200/JCO.2024.42.16\u suppl.11500。