喀斯特(G12C)抑制Sotorasib在先进的实体肿瘤。

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斯特里克勒JH香港DS, Fakih毫克,德赛J, Durm GA,夏皮罗GI, Falchook GS、价格TJ,萨赫,Denlinger CS,刘海YJ, Dy门将,克劳斯JC,久保Y,郭JC, Coveler,公园K, Kim TW Barlesi F,明斯特PN, Ramalingam党卫军,烧伤TF, Meric-Bernstam F, Henary H, Ngang J, Ngarmchamnanrith G,金正日J,胡克,佳能J, Lipford JR,弗里克,Lito P, Govindan R,李BT

喀斯特(G12C)抑制Sotorasib在先进的实体肿瘤。

郑传经地中海J。2020年9月24日,383 (13):1207 - 1217。doi: 10.1056 / NEJMoa1917239。Epub 2020 9月20。

PubMed ID

32955176 (在PubMed

]

文摘

背景:没有针对KRAS突变在癌症治疗已获批准。喀斯特p。G12C突变发生在13%的非小细胞肺癌(nsclc)和1到3%的结肠直肠癌和其他癌症。Sotorasib是一个选择性的小分子和不可逆转地目标喀斯特(G12C)。方法:我们进行了第一阶段试验sotorasib在晚期实体肿瘤患者窝藏喀斯特p。G12C突变。患者接受sotorasib每日口服一次。主要终点是安全。主要次级终点是药物动力学和客观的反应,根据反应评价标准作为评估在实体肿瘤(RECIST), 1.1版。结果:共有129名患者(与结直肠癌59与非小细胞肺癌,42岁,与其他肿瘤28)包含在剂量军团升级和扩张。病人收到平均3(范围,0到11)以前的抗癌治疗转移性疾病。 No dose-limiting toxic effects or treatment-related deaths were observed. A total of 73 patients (56.6%) had treatment-related adverse events; 15 patients (11.6%) had grade 3 or 4 events. In the subgroup with NSCLC, 32.2% (19 patients) had a confirmed objective response (complete or partial response) and 88.1% (52 patients) had disease control (objective response or stable disease); the median progression-free survival was 6.3 months (range, 0.0+ to 14.9 [with + indicating that the value includes patient data that were censored at data cutoff]). In the subgroup with colorectal cancer, 7.1% (3 patients) had a confirmed response, and 73.8% (31 patients) had disease control; the median progression-free survival was 4.0 months (range, 0.0+ to 11.1+). Responses were also observed in patients with pancreatic, endometrial, and appendiceal cancers and melanoma. CONCLUSIONS: Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation. Grade 3 or 4 treatment-related toxic effects occurred in 11.6% of the patients. (Funded by Amgen and others; CodeBreaK100 ClinicalTrials.gov number, NCT03600883.).

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药物

Sotorasib