WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell l...WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer(NSCLC)patients with ALK or ROS1 rearrangement.In the dose-escalation phase and dose-expansion phase,patients were treated with WX-0593 until disease progression,unacceptable toxicity,or subject withdrawal.In the dose-escalation phase,the primary endpoints were maximum tolerated dose(MTD),dose-limiting toxicity(DLT),and safety assessed by investigators.In the dose-expansion phase,the primary endpoint was objective response rate(ORR)assessed by investigators.Between September 25,2017 and October 15,2018,a total of 153 patients received WX-0593 treatment.Two dose-limiting toxicities(DLTs)including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient.MTD was not reached.Overall,140 of the 152(92%)patients experienced treatment-related adverse events(TRAEs)and 35 of the 152(23%)patients had TRAEs≥grade 3.The overall ORR was 59.3%(32 of 54)for the dose-escalation phase and 56.6%(56 of 99)for the dose-expansion phase.For patients who were ALK-rearranged and ALK TKI naive,the ORR were 81.0%(17 of 21)in the dose-escalation phase and 76.3%(29 of 38)in the dose-expansion phase,and for patients who previously received crizotinib as the only ALK TKI,the ORR were 38.1%(8 of 21)and 45.7%(21 of 46)for the two phases,respectively.For patients who were ROS1-rearranged,the ORR were 30.0%(3 of 10)in the dose-escalation phase and 44.4%(4 of 9)in the dose-expansion phase.WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.展开更多
基金This study(NCT03389815)was funded by Qilu Pharmaceutical Co.,Ltd.and also supported in part by China National Major Project for New Drug Innovation(2017ZX09304015)Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)(2016-I2M-1-001).
文摘WX-0593(Iruplinalkib)is a novel,highly selective oral ALK and ROS1 tyrosine kinase inhibitor(TKI).In this study,the safety,antitumor activity,and pharmacokinetics of WX-0593 were evaluated in advanced non-small cell lung cancer(NSCLC)patients with ALK or ROS1 rearrangement.In the dose-escalation phase and dose-expansion phase,patients were treated with WX-0593 until disease progression,unacceptable toxicity,or subject withdrawal.In the dose-escalation phase,the primary endpoints were maximum tolerated dose(MTD),dose-limiting toxicity(DLT),and safety assessed by investigators.In the dose-expansion phase,the primary endpoint was objective response rate(ORR)assessed by investigators.Between September 25,2017 and October 15,2018,a total of 153 patients received WX-0593 treatment.Two dose-limiting toxicities(DLTs)including one grade 3 QT interval prolonged and one grade 2 chronic heart failure were reported at the dose of 300 mg in one patient.MTD was not reached.Overall,140 of the 152(92%)patients experienced treatment-related adverse events(TRAEs)and 35 of the 152(23%)patients had TRAEs≥grade 3.The overall ORR was 59.3%(32 of 54)for the dose-escalation phase and 56.6%(56 of 99)for the dose-expansion phase.For patients who were ALK-rearranged and ALK TKI naive,the ORR were 81.0%(17 of 21)in the dose-escalation phase and 76.3%(29 of 38)in the dose-expansion phase,and for patients who previously received crizotinib as the only ALK TKI,the ORR were 38.1%(8 of 21)and 45.7%(21 of 46)for the two phases,respectively.For patients who were ROS1-rearranged,the ORR were 30.0%(3 of 10)in the dose-escalation phase and 44.4%(4 of 9)in the dose-expansion phase.WX-0593 showed favorable safety and promising antitumor activity in advanced NSCLC patients with ALK or ROS1 rearrangement.
