Abstract：
UNASSIGNED: The study was to determine the activity and safety of the TGF-β inhibitor vactosertib in combination with imatinib in patients with desmoid tumors.
UNASSIGNED: In this investigator-initiated, open-label, multicenter, phase Ib/II trial, patients with desmoid tumors not amenable to locoregional therapies (surgery and/or radiotherapy) or with disease progression following at least one treatment were enrolled. Participants were administered 400 mg imatinib daily in combination with vactosertib (5 days on and 2 days off, twice a day) every 28 days. In phase Ib, the vactosertib dose was set at 100 mg (level -1) and 200 mg (level 1) to determine the recommended phase II dose (RP2D). Phase II assessed the efficacy, with the primary endpoint being progression-free rate (PFR) at 16 weeks.
UNASSIGNED: No dose-limiting toxicities were observed during phase Ib; therefore RP2D was defined at doses of 400 mg imatinib daily in combination with 200 mg vactosertib. Of the 27 patients evaluated, 7 (25.9%) achieved a confirmed partial response and 19 (70.4%) were stable. The PFR at 16 weeks and 1 year were 96.3% and 81.0%, respectively. Most toxicities were mild to moderate myalgia (n = 10, 37%), anemia (n = 10, 37%), and nausea (n = 9, 33.3%). Common grade 3 to 4 toxicities included neutropenia (n = 6, 22.2%) and anemia (n = 5, 18.5%).
UNASSIGNED: The vactosertib and imatinib combination was well tolerated, with promising clinical activity in patients with progressive, locally advanced desmoid tumors. This is the first study investigating a novel target agent, a TGF-β inhibitor, in this rare and difficult-to-treat desmoid tumor.
UNASSIGNED: In this investigator-initiated, open-label, multicenter, phase Ib/II trial, patients with desmoid tumors not amenable to locoregional therapies (surgery and/or radiotherapy) or with disease progression following at least one treatment were enrolled. Participants were administered 400 mg imatinib daily in combination with vactosertib (5 days on and 2 days off, twice a day) every 28 days. In phase Ib, the vactosertib dose was set at 100 mg (level -1) and 200 mg (level 1) to determine the recommended phase II dose (RP2D). Phase II assessed the efficacy, with the primary endpoint being progression-free rate (PFR) at 16 weeks.
UNASSIGNED: No dose-limiting toxicities were observed during phase Ib; therefore RP2D was defined at doses of 400 mg imatinib daily in combination with 200 mg vactosertib. Of the 27 patients evaluated, 7 (25.9%) achieved a confirmed partial response and 19 (70.4%) were stable. The PFR at 16 weeks and 1 year were 96.3% and 81.0%, respectively. Most toxicities were mild to moderate myalgia (n = 10, 37%), anemia (n = 10, 37%), and nausea (n = 9, 33.3%). Common grade 3 to 4 toxicities included neutropenia (n = 6, 22.2%) and anemia (n = 5, 18.5%).
UNASSIGNED: The vactosertib and imatinib combination was well tolerated, with promising clinical activity in patients with progressive, locally advanced desmoid tumors. This is the first study investigating a novel target agent, a TGF-β inhibitor, in this rare and difficult-to-treat desmoid tumor.
摘要：
■该研究是为了确定TGF-β抑制剂vactosertib与伊马替尼联合用于韧带样肿瘤患者的活性和安全性。
■在这个研究者发起的，开放标签，多中心，Ib/II期试验，纳入了不适合局部区域治疗(手术和/或放疗)或至少一次治疗后疾病进展的纤维瘤患者.参与者每天服用400毫克伊马替尼与vactosertib（5天和2天休息，一天两次)每28天。在Ib阶段,vactosertib剂量设定为100mg(水平-1)和200mg(水平1),以确定推荐的II期剂量(RP2D).第二阶段评估了疗效，主要终点是16周时的无进展率（PFR）。
■在Ib期未观察到剂量限制性毒性;因此RP2D定义为每天400mg伊马替尼与200mgvactosertib组合的剂量。在评估的27名患者中，7（25.9％）获得确认的部分反应，19（70.4％）稳定。16周和1年的PFR分别为96.3%和81.0%,分别。大多数毒性是轻度至中度肌痛（n=10，37％），贫血（n=10，37%），恶心（n=9，33.3%）。常见的3至4级毒性包括中性粒细胞减少症（n=6，22.2%）和贫血（n=5，18.5%）。
■vactosertib和伊马替尼联合用药耐受性良好，在进行性患者中具有有希望的临床活动，局部晚期硬纤维瘤。这是第一个研究新的目标剂，TGF-β抑制剂，在这种罕见且难以治疗的硬纤维瘤中。
■在这个研究者发起的，开放标签，多中心，Ib/II期试验，纳入了不适合局部区域治疗(手术和/或放疗)或至少一次治疗后疾病进展的纤维瘤患者.参与者每天服用400毫克伊马替尼与vactosertib（5天和2天休息，一天两次)每28天。在Ib阶段,vactosertib剂量设定为100mg(水平-1)和200mg(水平1),以确定推荐的II期剂量(RP2D).第二阶段评估了疗效，主要终点是16周时的无进展率（PFR）。
■在Ib期未观察到剂量限制性毒性;因此RP2D定义为每天400mg伊马替尼与200mgvactosertib组合的剂量。在评估的27名患者中，7（25.9％）获得确认的部分反应，19（70.4％）稳定。16周和1年的PFR分别为96.3%和81.0%,分别。大多数毒性是轻度至中度肌痛（n=10，37％），贫血（n=10，37%），恶心（n=9，33.3%）。常见的3至4级毒性包括中性粒细胞减少症（n=6，22.2%）和贫血（n=5，18.5%）。
■vactosertib和伊马替尼联合用药耐受性良好，在进行性患者中具有有希望的临床活动，局部晚期硬纤维瘤。这是第一个研究新的目标剂，TGF-β抑制剂，在这种罕见且难以治疗的硬纤维瘤中。
