[Translation] A Phase 1/1b, open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics and anti-tumor activity of KIN-2787 in patients with BRAF and/or NRAS mutation-positive solid tumors
A1部分:
主要目的是确定KIN-2787口服给药治疗BRAF突变阳性晚期或转移性实体瘤受试者或NRAS突变黑色素瘤受试者的安全性、耐受性及DLT;并确定MTD和/或在剂量扩展部分(B部分)进行进一步临床研究的合适剂量。
次要目的包括表征KIN-2787的PK特性以及食物对KIN-2787 PK的影响。
探索性目的包括额外的KIN-2787 PK表征、评价KIN-2787对生存期和其他至事件发生时间终点的影响、采用血液样本和肿瘤活检样本估计KIN-2787的PD作用、 基因型评估, 以及评估治疗期间基因型变化对结局的影响。
B部分:
主要目的是评估KIN-2787治疗II类或III类BRAF基因组改变晚期或转移性实体瘤受试者的抗肿瘤活性的初步证据。
次要目的为进一步评价RP2D剂量水平下KIN-2787的安全性、耐受性和PK特征。
探索性目的包括额外的 KIN-2787 PK表征、评价KIN-2787对生存期和其他至事件发生时间终点的影响、采用血液样本和肿瘤活检样本估计KIN-2787的PD作用、 基因型评估, 以及治疗期间基因型变化对结局的影响以及对患者报告结局(PRO)指标的影响。
[Translation] Part A1:
The primary objective is to determine the safety, tolerability, and DLT of oral administration of KIN-2787 in subjects with BRAF mutation-positive advanced or metastatic solid tumors or NRAS-mutant melanoma; and to determine the MTD and/or in dose expansion Part (Part B) conduct further clinical studies on appropriate dosages.
Secondary objectives include characterizing the PK properties of KIN-2787 and the impact of food on KIN-2787 PK.
Exploratory objectives include additional PK characterization of KIN-2787, evaluation of the impact of KIN-2787 on survival and other time-to-event endpoints, estimation of the PD effect of KIN-2787 using blood samples and tumor biopsy samples, genotypic assessment, and evaluation Impact of genotypic changes during treatment on outcome.
Part B:
The primary objective is to evaluate preliminary evidence of anti-tumor activity of KIN-2787 in subjects with class II or class III BRAF genome-altered advanced or metastatic solid tumors.
The secondary objective is to further evaluate the safety, tolerability and PK characteristics of KIN-2787 at the RP2D dose level.
Exploratory objectives include additional PK characterization of KIN-2787, evaluation of the impact of KIN-2787 on survival and other time-to-event endpoints, estimation of the PD effect of KIN-2787 using blood samples and tumor biopsy samples, genotype assessment, and treatment The impact of genotypic changes over time on outcomes and on patient-reported outcome (PRO) measures.