Tenosynovial giant cell tumour (TGCT) is a locally aggressive neoplasm for which few systemic treatment options exist. This study evaluated the efficacy and safety of vimseltinib, an oral, switch-control, CSF1R inhibitor, in patients with symptomatic TGCT not amenable to surgery. MOTION is a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial done in 35 specialised hospitals in 13 countries. Eligible patients were adults (aged ≥18 years) with a histologically confirmed diagnosis of TGCT for which surgical resection could potentially worsen functional limitation or cause severe morbidity. Patients were randomly assigned (2:1) with interactive response technology to vimseltinib (30 mg orally twice weekly) or placebo, administrated in 28-day cycles for 24 weeks. Patients and site personnel were masked to treatment assignment until week 25, unless progressive disease was confirmed earlier. The primary endpoint was objective response rate by independent radiological review using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST) at week 25 in the intention-to-treat population. Safety was assessed in all patients who received the study drug. The trial is registered with , , and enrolment is complete. Between Jan 21, 2022, and Feb 21, 2023, 123 patients were randomly assigned (83 to vimseltinib and 40 to placebo). 73 (59%) patients were female and 50 (41%) were male. Nine (11%) of 83 patients assigned to vimseltinib and five (13%) of 40 patients assigned to placebo discontinued treatment before week 25; one patient in the placebo group did not receive any study drug. Objective response rate per RECIST was 40% (33 of 83 patients) in the vimseltinib group 0% (none of 40) in the placebo group (difference 40% [95% CI 29–51]; p<0·0001). Most treatment-emergent adverse events (TEAEs) were grade 1 or 2; the only grade 3 or 4 TEAE that occurred in more than 5% of patients receiving vimseltinib was increased blood creatine phosphokinase (eight [10%] of 83). One patient in the vimseltinib group had a treatment-related serious TEAE of subcutaneous abscess. No evidence of cholestatic hepatotoxicity or drug-induced liver injury was noted. Vimseltinib produced a significant objective response rate and clinically meaningful functional and symptomatic improvement in patients with TGCT, providing an effective treatment option for these patients. Deciphera Pharmaceuticals.

中文翻译：

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Vimseltinib 与安慰剂治疗腱滑膜巨细胞瘤 (MOTION)：一项多中心、随机、双盲、安慰剂对照 3 期试验


腱鞘巨细胞瘤（TGCT）是一种局部侵袭性肿瘤，几乎没有全身治疗选择。本研究评估了 Vimseltinib（一种口服开关控制 CSF1R 抑制剂）对于患有不适合手术的有症状 TGCT 患者的疗效和安全性。 MOTION 是一项多中心、随机、双盲、安慰剂对照的 3 期试验，在 13 个国家的 35 家专科医院进行。符合资格的患者是经组织学确诊为 TGCT 的成年人（年龄≥18 岁），手术切除可能会加重功能限制或导致严重的发病率。采用交互式反应技术将患者随机分配 (2:1) 治疗 vimseltinib（每次口服 30 毫克，每周两次）或安慰剂，以 28 天为一个周期，持续 24 周。除非较早确认疾病进展，否则患者和现场工作人员在第 25 周之前均不知道治疗分配情况。主要终点是在意向治疗人群中使用实体瘤反应评估标准 1.1 版 (RECIST) 在第 25 周通过独立放射学审查得出的客观反应率。对所有接受研究药物的患者进行安全性评估。试验已通过 、 注册，注册已完成。 2022年1月21日至2023年2月21日期间，123名患者被随机分配（83名接受vimseltinib治疗，40名接受安慰剂）。 73 名患者（59%）为女性，50 名患者（41%）为男性。分配至 vimseltinib 的 83 名患者中的 9 名 (11%) 和分配至安慰剂的 40 名患者中的 5 名 (13%) 在第 25 周之前停止了治疗；安慰剂组的一名患者没有接受任何研究药物。 Vimseltinib 组的 RECIST 客观缓解率为 40%（83 例患者中的 33 例），而安慰剂组为 0%（40 例患者中均无）（差异 40% [95% CI 29–51]；p<0·0001）。 大多数治疗引起的不良事件 (TEAE) 为 1 级或 2 级；在接受维赛替尼治疗的患者中，超过 5% 发生的唯一 3 级或 4 级 TEAE 是血液肌酸磷酸激酶升高（83 例患者中，有 8 例 [10%]）。 vimseltinib 组中的一名患者出现与治疗相关的严重 TEAE 皮下脓肿。没有发现胆汁淤积性肝毒性或药物性肝损伤的证据。 Vimseltinib 在 TGCT 患者中产生了显着的客观缓解率以及具有临床意义的功能和症状改善，为这些患者提供了有效的治疗选择。德西菲拉制药公司。