A dose-escalation and expansion,phase 1/2 study(ClinicalTrials.gov,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer(NSCLC).H...A dose-escalation and expansion,phase 1/2 study(ClinicalTrials.gov,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer(NSCLC).Here,we report results from the phase 1 portion.Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks.Dose escalation followed a Bayesian logistic regression model that included overdose control,with subsequent selection of tolerable levels for dose expansion.Overall,63 patients were enrolled,including 43 receiving a recommended dose for expansion of 4.8 mg/kg.All patients had HER2-mutant disease.Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort.Grade≥3 treatment-related adverse events occurred in 29(46.0%)patients.One patient in the 6.4 mg/kg cohort died due to interstitial lung disease.As of April 11,2023,the 4.8 mg/kg cohort showed an objective response rate of 41.9%(95%Cl 27.0-57.9),and a disease control rate of 95.3%(95%Cl 84.2-99.4).The median duration of response was 13.7 months,with 13 of 18 responses ongoing.The median progression-free survival was 8.4 months(95%CI 7.1-15.0).SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutantNSCLC.展开更多
基金This study was funded by Jiangsu Hengrui Pharmaceuticals.
文摘A dose-escalation and expansion,phase 1/2 study(ClinicalTrials.gov,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer(NSCLC).Here,we report results from the phase 1 portion.Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks.Dose escalation followed a Bayesian logistic regression model that included overdose control,with subsequent selection of tolerable levels for dose expansion.Overall,63 patients were enrolled,including 43 receiving a recommended dose for expansion of 4.8 mg/kg.All patients had HER2-mutant disease.Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort.Grade≥3 treatment-related adverse events occurred in 29(46.0%)patients.One patient in the 6.4 mg/kg cohort died due to interstitial lung disease.As of April 11,2023,the 4.8 mg/kg cohort showed an objective response rate of 41.9%(95%Cl 27.0-57.9),and a disease control rate of 95.3%(95%Cl 84.2-99.4).The median duration of response was 13.7 months,with 13 of 18 responses ongoing.The median progression-free survival was 8.4 months(95%CI 7.1-15.0).SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutantNSCLC.
