Nab-paclitaxel plus gemcitabine(AG)is the standard first-line chemotherapy for advanced or metastatic pancreatic ductal adenocarcinoma and has limited efficacy.This phase 1b/2 study aimed to evaluate SHR-1701(an anti-...Nab-paclitaxel plus gemcitabine(AG)is the standard first-line chemotherapy for advanced or metastatic pancreatic ductal adenocarcinoma and has limited efficacy.This phase 1b/2 study aimed to evaluate SHR-1701(an anti-PD-L1/TGF-βRII fusion protein)plus AG in this population(NCT04624217).In phase 1b part,the recommended dose of SHR-1701 was identified as 30 mg/kg every 3 weeks,when combined with AG.In phase 2 part,the primary endpoint was objective response rate(ORR).As of Mar 31,2023,56 patients were enrolled.Median follow-up was 10.3 months(range,0.2–24.7).ORR was 32.1%(95%CI,20.3–46.0).Median progressive-free survival(PFS)was 5.6 months(95%CI,4.3–6.6),and median overall survival(OS)was 10.3 months(95%CI,8.8–12.3).Treatment-related adverse events of grade≥3 were reported in 27(48.2%)patients,with the most common being decreased neutrophil count.Patients with PD-L1 TPS≥1%showed a higher ORR(66.7%vs.25.0%),as well as extended median PFS(6.3 vs.5.3 months)and median OS(18.8 vs.9.9 months).Additionally,reduction of CA19-9 by at least 80%during treatment and pSMAD2/3 staining intensity of 1+at baseline were potential monitoring tools and predictive biomarkers for better clinical outcomes,respectively.Tumor-specific T-cell infiltration and pancreatic cancer tumor subtypes were associated with anti-tumor response.The interactions within tumor microenvironment were involved disease progression.Overall,first-line SHR-1701 plus AG showed promising anti-tumor activity and controllable safety in advanced or metastatic pancreatic ductal adenocarcinoma,and features of patients more likely to benefit from the combination were drawn.展开更多
文摘Nab-paclitaxel plus gemcitabine(AG)is the standard first-line chemotherapy for advanced or metastatic pancreatic ductal adenocarcinoma and has limited efficacy.This phase 1b/2 study aimed to evaluate SHR-1701(an anti-PD-L1/TGF-βRII fusion protein)plus AG in this population(NCT04624217).In phase 1b part,the recommended dose of SHR-1701 was identified as 30 mg/kg every 3 weeks,when combined with AG.In phase 2 part,the primary endpoint was objective response rate(ORR).As of Mar 31,2023,56 patients were enrolled.Median follow-up was 10.3 months(range,0.2–24.7).ORR was 32.1%(95%CI,20.3–46.0).Median progressive-free survival(PFS)was 5.6 months(95%CI,4.3–6.6),and median overall survival(OS)was 10.3 months(95%CI,8.8–12.3).Treatment-related adverse events of grade≥3 were reported in 27(48.2%)patients,with the most common being decreased neutrophil count.Patients with PD-L1 TPS≥1%showed a higher ORR(66.7%vs.25.0%),as well as extended median PFS(6.3 vs.5.3 months)and median OS(18.8 vs.9.9 months).Additionally,reduction of CA19-9 by at least 80%during treatment and pSMAD2/3 staining intensity of 1+at baseline were potential monitoring tools and predictive biomarkers for better clinical outcomes,respectively.Tumor-specific T-cell infiltration and pancreatic cancer tumor subtypes were associated with anti-tumor response.The interactions within tumor microenvironment were involved disease progression.Overall,first-line SHR-1701 plus AG showed promising anti-tumor activity and controllable safety in advanced or metastatic pancreatic ductal adenocarcinoma,and features of patients more likely to benefit from the combination were drawn.
