未经授权:c-MET是各种癌症的重要治疗靶点;然而,中华人民共和国目前仅零售一种特异性c-MET抑制剂。我们的临床前研究揭示了HS-10241抑制c-MET的高选择性。这项第一阶段的研究旨在评估安全性,耐受性,药代动力学,选择性c-MET抑制剂(HS-10241)在晚期实体瘤患者中的抗肿瘤活性。
UNASSIGNED:局部晚期或转移性实体瘤患者口服单剂量或多剂量HS-10241,每天一次或每天两次,连续21天,其中包括以下六个方案:每天100毫克,200毫克,每天一次,400毫克,每天一次,600毫克,每天一次,200毫克,每天两次,每天两次300毫克。治疗一直持续到疾病进展,不可接受的毒性,或治疗终止。主要终点是剂量限制性毒性和最大耐受剂量(MTD)的发生率。次要终点包括安全性,耐受性,药代动力学,和药效学。
UNASSIGNED:共有27例晚期非小细胞肺癌患者接受HS-10241,3例患者在每天一次600mgHS-10241治疗后观察到剂量限制性毒性。每日一次给药,MTD为400毫克,每天两次给药,最大安全递增剂量为300毫克,未达到MTD。恶心(48.1%,13of27),疲劳(37.0%,10of27),贫血(33.3%,27个中的9个)是三个最常见的治疗引起的不良事件。每天一次400毫克,Css,最大值为5076ng/mL,稳态曲线下面积为39,998h×ng/mL。MET阳性的患者(n=5)(MET外显子14跳跃,MET扩增,和MET免疫组织化学3+)已确认部分反应(n=1)或疾病稳定(n=3),疾病控制率为80.0%。
UNASSIGNED:选择性c-MET抑制剂HS-10241在晚期非小细胞肺癌中具有良好的耐受性和临床活性,尤其是MET阳性的患者。此外,本研究阐述了HS-10241在癌症患者中的治疗潜力。
UNASSIGNED: c-MET is an important therapeutic target for various cancers; however, the People\'s Republic of China currently retails only one specific c-MET inhibitor. Our preclinical
study has revealed the high selectivity of HS-10241 to suppress c-MET. This phase 1
study aims to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of the selective c-MET inhibitor (HS-10241) in patients with advanced solid tumors.
UNASSIGNED: Patients with locally advanced or metastatic solid tumors orally received a single or multiple dose of HS-10241 once daily or twice daily for 21 consecutive days, which included the following six regimens: 100 mg once daily, 200 mg once daily, 400 mg once daily, 600 mg once daily, 200 mg twice daily, and 300 mg twice daily. The treatment continued until disease progression, unacceptable toxicity, or treatment termination. The primary end point was the incidence of dose-limiting toxicity and maximal tolerated dose (MTD). Secondary end points included safety, tolerability, pharmacokinetics, and pharmacodynamics.
UNASSIGNED: A total of 27 patients with advanced NSCLC received HS-10241, and dose-limiting toxicity was observed in three patients after 600 mg once-daily HS-10241 treatment. For once-daily dosing, MTD was 400 mg, and for twice-daily dosing, the maximal safe escalated dose was 300 mg, and MTD was not reached. Nausea (48.1%, 13 of 27), fatigue (37.0%, 10 of 27), and anemia (33.3%, 9 of 27) are the three most frequent treatment-emergent adverse events. At 400 mg once daily, Css,max was 5076 ng/mL and steady state area under the curve was 39,998 h × ng/mL. Patients (n = 5) with positive MET (MET exon 14-skipping, MET amplified, and MET immunohistochemistry 3+) had confirmed partial responses (n = 1) or stable disease (n = 3), with a disease control rate of 80.0%.
UNASSIGNED: The selective c-MET inhibitor HS-10241 was well tolerated and had clinical activity in advanced NSCLC, especially in patients with positive MET. Furthermore, this
study expounds on the therapeutic potential of HS-10241 in patients with cancer.