[Translation] Phase I clinical study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of NP-01 tablets in the treatment of patients with advanced malignant solid tumors
主要目的:1)确定NP-01 片在晚期恶性实体瘤患者中的剂量限制性毒性(DLT)和最大耐受剂量(MTD)和/或确定NP-01 片的后续研究推荐剂量;2)评价NP-01 片在晚期恶性实体瘤患者中的安全性和耐受性。次要目的:1)评价NP-01 片在晚期恶性实体瘤患者中的药代动力学特征,为后续的临床研究提供依据;2)按照RECIST1.1 标准,观察客观缓解率(ORR)、疾病控制率(DCR)和无进展生存期(PFS),初步评估NP-01 片治疗晚期恶性实体瘤患者的疗效。探索性目的:1)以血清VEGF 等指标,初步探索构建PK/PD 模型,并初步探索临床预测模型,模拟不同剂量临床疗效与安全性,为下一步临床方案的制定提供支持;2)仅扩展阶段:以客观缓解率(ORR)为临床终点初步探索在以不同生物标记物为指标的肿瘤患者中的疗效,潜在的生物标记物包括Met、KDR(组织)等。3)仅扩展阶段:探索NP-01 片对不同的实体瘤患者生物标记物的敏感性及机制。
[Translation] Main objectives: 1) To determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of NP-01 tablets in patients with advanced malignant solid tumors and/or to determine the recommended dose of NP-01 tablets for follow-up studies; 2) Evaluation Safety and tolerability of NP-01 tablets in patients with advanced malignant solid tumors. Secondary objectives: 1) To evaluate the pharmacokinetic characteristics of NP-01 tablets in patients with advanced malignant solid tumors, and to provide a basis for subsequent clinical research; 2) To observe the objective response rate (ORR), disease Control rate (DCR) and progression-free survival (PFS), preliminarily evaluate the efficacy of NP-01 tablets in the treatment of patients with advanced malignant solid tumors. Exploratory purposes: 1) Use serum VEGF and other indicators to initially explore the establishment of a PK/PD model, and initially explore a clinical prediction model, simulate the clinical efficacy and safety of different doses, and provide support for the formulation of the next clinical program; 2) Only expand Stage: Using objective response rate (ORR) as the clinical endpoint to initially explore the efficacy in tumor patients with different biomarkers as indicators, potential biomarkers include Met, KDR (tissue), etc. 3) Expansion stage only: to explore the sensitivity and mechanism of NP-01 tablets to different biomarkers in patients with solid tumors.