[Translation] A Phase I/II clinical study of the tolerability, safety, efficacy and pharmacokinetics of ZG19018 in patients with advanced solid tumors harboring KRAS G12C mutations with dose escalation and expansion
主要目的:考察ZG19018治疗至少经一线标准治疗失败、不耐受或无标准治疗的携带KRAS G12C突变的晚期实体瘤患者的安全性和耐受性,并考察在设定剂量中可能出现的剂量限制性毒性和最大耐受剂量;研究推荐剂量下低脂饮食对ZG19018代谢的影响;考察ZG19018治疗经至少一线标准治疗失败的携带KRAS G12C突变的晚期非小细胞肺癌、晚期结直肠癌及其他晚期实体瘤患者的有效性。次要目的:考察ZG19018治疗至少经一线标准治疗失败、不耐受或无标准治疗的携带KRAS G12C突变的晚期实体瘤患者的药代动力学特征;考察ZG19018治疗至少经一线标准治疗失败、不耐受或无标准治疗的携带KRAS G12C突变的晚期实体瘤患者的有效性;探索ZG19018的II期推荐剂量以及ZG19018在人体的代谢途径;考察ZG19018治疗经至少一线标准治疗失败的携带KRAS G12C突变的晚期非小细胞肺癌、晚期结直肠癌及其他晚期实体瘤患者的安全性及药代动力学特征;分析潜在的生物标志物与疗效的关系。
[Translation] Main objectives: To investigate the safety and tolerability of ZG19018 in the treatment of patients with advanced solid tumors carrying KRAS G12C mutation who have failed at least one line of standard treatment, are intolerant or have no standard treatment, and to investigate the dose-limiting toxicity and maximum tolerated dose that may occur at the set dose; to study the effect of a low-fat diet on the metabolism of ZG19018 at the recommended dose; to investigate the effectiveness of ZG19018 in the treatment of patients with advanced non-small cell lung cancer, advanced colorectal cancer and other advanced solid tumors carrying KRAS G12C mutation who have failed at least one line of standard treatment. Secondary objectives: To investigate the pharmacokinetic characteristics of ZG19018 in the treatment of patients with advanced solid tumors carrying KRAS G12C mutation who have failed at least one line of standard treatment, are intolerant or have no standard treatment; to investigate the effectiveness of ZG19018 in the treatment of patients with advanced solid tumors carrying KRAS G12C mutation who have failed at least one line of standard treatment, are intolerant or have no standard treatment; to explore the recommended Phase II dose of ZG19018 and the metabolic pathway of ZG19018 in humans; to investigate the safety and pharmacokinetic characteristics of ZG19018 in the treatment of patients with advanced non-small cell lung cancer, advanced colorectal cancer and other advanced solid tumors carrying KRAS G12C mutation who have failed at least one line of standard treatment; and to analyze the relationship between potential biomarkers and efficacy.