作用机制

 

SHP2,也称为PTPN11,是一种磷酸酶,能够对底物蛋白去磷酸化,是调控细胞功能的重要分子。在RTK通路中,SHP2位于RAS上游,介导肿瘤增殖; 同时SHP2位于免疫检查点PD-1的下游,抑制T细胞抗肿瘤作用;还处在CSF-1R下游,促进肿瘤相关巨噬细胞功能。因此,靶向SHP2可起到多重抗肿瘤作用。

 

JAB-3312作为高选择性SHP2磷酸酶变构抑制剂,可以阻断RTK/RAS/MAPK信号通路,抑制RTK驱动或KRAS、BRAF Class 3、NF1功能缺失突变的肿瘤细胞的生长和增殖;同时JAB-3312可以阻断PD-1抑制信号,增强CD8+T细胞杀伤功能,并通过抑制肿瘤相关巨噬细胞功能来解除肿瘤微环境中的免疫抑制,从而发挥抗肿瘤作用。

适应症

120
患者受益

现有研究表明,JAB-3312可能对具有某些特定基因突变的非小细胞肺癌头颈鳞癌食管鳞癌结直肠癌胰腺癌的患者有效,以及患有第三类BRAF突变NF1功能缺失突变实体瘤的患者或能从中获益。 从2019年的全球肿瘤发病数据估算,全球120万晚期实体瘤者有望从SHP2抑制剂单药疗法中受益。此外,SHP2抑制剂已显示出与多种靶向疗法和免疫疗法有协同作用,如靶向KRAS、EGFR、ALK、PD-1等。

临床试验

联合疗法


药物

联合用药搭档

地区

试验阶段

适应症

登记信息

JAB-3312

戈来雷塞 (KRAS G12Ci)

中国 IIa期 晚期实体瘤

ClinicalTrials: NCT05288205

CDE Number: CTR20220587

JAB-3312+戈来雷塞 VS 替雷利珠单抗+培美曲塞+卡铂 中国

III期

非小细胞肺癌

ClinicalTrials: NCT06416410

 

 

参考文献

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