Mutations in the KRAS gene have long been implicated in the pathogenesis of colorectal cancer(CRC).KRAS G12C inhibitors overcome the“undruggable”challenge,enabling precision therapy.Garsorasib(D-1553),a highly poten...Mutations in the KRAS gene have long been implicated in the pathogenesis of colorectal cancer(CRC).KRAS G12C inhibitors overcome the“undruggable”challenge,enabling precision therapy.Garsorasib(D-1553),a highly potent and selective KRAS G12C inhibitor,has demonstrated promising anti-tumor activity and favorable safety profile in early clinical trials.We conducted an openlabel,nonrandomized phase II trial(ClinicalTrials.gov,NCT04585035)to assess the safety and efficacy of garsorasib with or without cetuximab in KRAS G12C-mutated CRC.In the monotherapy cohort(n=26),objective response rate(ORR)was 19.2%(95%CI,6.6-39.4),disease control rate(DCR)was 92.3%(95%CI,74.9-99.1),median progression-free survival(PFS)was 5.5 months(95%CI,2.9-11.6)and median overall survival(OS)was 13.1 months(95%CI,9.5-NE).In the combination cohort(n=42),ORR was 45.2%(95%CI,29.8-61.3),DCR was 92.9%(95%CI,80.5-98.5),median PFS was 7.5 months(95%CI,5.5-8.1),and median OS was not reached.Grade≥3 treatment-related adverse events occurred in 5(19.2%)and 6(14.3%)patients in monotherapy and combination cohort,respectively.Garsorasib with or without cetuximab showed a promising efficacy and manageable safety profiles in heavily pretreated patients with KRAS G12C-mutated CRC,providing a potential new treatment approach for such population.展开更多
基金sponsored by InventisBio.Medical writing assistance for this manuscript was provided by Xinying Liu from InventisBio.
文摘Mutations in the KRAS gene have long been implicated in the pathogenesis of colorectal cancer(CRC).KRAS G12C inhibitors overcome the“undruggable”challenge,enabling precision therapy.Garsorasib(D-1553),a highly potent and selective KRAS G12C inhibitor,has demonstrated promising anti-tumor activity and favorable safety profile in early clinical trials.We conducted an openlabel,nonrandomized phase II trial(ClinicalTrials.gov,NCT04585035)to assess the safety and efficacy of garsorasib with or without cetuximab in KRAS G12C-mutated CRC.In the monotherapy cohort(n=26),objective response rate(ORR)was 19.2%(95%CI,6.6-39.4),disease control rate(DCR)was 92.3%(95%CI,74.9-99.1),median progression-free survival(PFS)was 5.5 months(95%CI,2.9-11.6)and median overall survival(OS)was 13.1 months(95%CI,9.5-NE).In the combination cohort(n=42),ORR was 45.2%(95%CI,29.8-61.3),DCR was 92.9%(95%CI,80.5-98.5),median PFS was 7.5 months(95%CI,5.5-8.1),and median OS was not reached.Grade≥3 treatment-related adverse events occurred in 5(19.2%)and 6(14.3%)patients in monotherapy and combination cohort,respectively.Garsorasib with or without cetuximab showed a promising efficacy and manageable safety profiles in heavily pretreated patients with KRAS G12C-mutated CRC,providing a potential new treatment approach for such population.
