Adding a PD-1/PD-L1 inhibitor to gemcitabine plus cisplatin(GemCis)has shown survival benefits in advanced biliary tract cancer(BTC).Dual inhibition of PD-1/PD-L1 and TIGIT may act synergistically,and further enhance ...Adding a PD-1/PD-L1 inhibitor to gemcitabine plus cisplatin(GemCis)has shown survival benefits in advanced biliary tract cancer(BTC).Dual inhibition of PD-1/PD-L1 and TIGIT may act synergistically,and further enhance antitumor effects.ZSAB-TOP was a single-arm,multicenter,phase 2 study(NCT05023109)evaluating efficacy and safety of first-line tislelizumab(a PD-1 inhibitor)plus ociperlimab(a TIGIT inhibitor)and GemCis in advanced BTC.Eligible patients received tislelizumab(200 mg)and ociperlimab(900 mg)on day 1 until unacceptable toxicity or disease progression,in combination with cisplatin(25 mg/m^(2))and gemcitabine(1000 mg/m^(2))on days 1 and 8 of a 21-day cycle for a maximum eight cycles.The primary endpoint was confirmed objective response rate(ORR)evaluated by the investigator,which was compared with a historical ORR of 25%with GemCis,with a statistical superiority setting at p≤0.05.From March 8,2022,to January 18,2023,45 patients were enrolled.Among the 41 patients in the efficacy analysis set,the confirmed ORR was 51.2%(95%CI 35.1–67.1),achieving the statistical superiority criteria(p=0.0003).Patients who had TIGIT^(+)/PD-L1^(+)(n=16)tended to have a numerically greater confirmed ORR(75.0%[95%CI 47.6–92.7]).After a median follow-up of 14.6 months,median progression-free survival was 7.7 months(95%CI 6.0–9.4),with a median overall survival of 17.4 months(95%CI 11.7-not reached).Treatment-related adverse events of grade≥3 occurred in 60.0%of patients;immune-mediated adverse events of any grade was observed in 42.2%,with the majority being grade 1 or 2.In conclusion,first-line tislelizumab and ociperlimab plus GemCis yielded clinically promising tumor response and survival outcomes in advanced BTC and were generally well tolerated without new safety signals.展开更多
基金supported by the Program of Shanghai Academic Research Leader(22XD1402700)BeiGene(Beijing)Co.,Ltd.
文摘Adding a PD-1/PD-L1 inhibitor to gemcitabine plus cisplatin(GemCis)has shown survival benefits in advanced biliary tract cancer(BTC).Dual inhibition of PD-1/PD-L1 and TIGIT may act synergistically,and further enhance antitumor effects.ZSAB-TOP was a single-arm,multicenter,phase 2 study(NCT05023109)evaluating efficacy and safety of first-line tislelizumab(a PD-1 inhibitor)plus ociperlimab(a TIGIT inhibitor)and GemCis in advanced BTC.Eligible patients received tislelizumab(200 mg)and ociperlimab(900 mg)on day 1 until unacceptable toxicity or disease progression,in combination with cisplatin(25 mg/m^(2))and gemcitabine(1000 mg/m^(2))on days 1 and 8 of a 21-day cycle for a maximum eight cycles.The primary endpoint was confirmed objective response rate(ORR)evaluated by the investigator,which was compared with a historical ORR of 25%with GemCis,with a statistical superiority setting at p≤0.05.From March 8,2022,to January 18,2023,45 patients were enrolled.Among the 41 patients in the efficacy analysis set,the confirmed ORR was 51.2%(95%CI 35.1–67.1),achieving the statistical superiority criteria(p=0.0003).Patients who had TIGIT^(+)/PD-L1^(+)(n=16)tended to have a numerically greater confirmed ORR(75.0%[95%CI 47.6–92.7]).After a median follow-up of 14.6 months,median progression-free survival was 7.7 months(95%CI 6.0–9.4),with a median overall survival of 17.4 months(95%CI 11.7-not reached).Treatment-related adverse events of grade≥3 occurred in 60.0%of patients;immune-mediated adverse events of any grade was observed in 42.2%,with the majority being grade 1 or 2.In conclusion,first-line tislelizumab and ociperlimab plus GemCis yielded clinically promising tumor response and survival outcomes in advanced BTC and were generally well tolerated without new safety signals.
