Discussion
tumor, TEAEs
TUMOR, HYPERTENSION
This open-label, phase 1/1b study was conducted to evaluate the safety, tolerability, PK characteristics, and preliminary anticancer activity at the RP2D of fruquintinib in U.S. patients to confirm the RP2D established in China. Fruquintinib was well tolerated in both the 3 and 5 mg dose cohorts. One DLT (grade 4 hypertension) was observed in the 3 mg dose cohort, and no DLTs were observed in the 5 mg dose cohort. The RP2D was established as 5 mg PO, 3/1, on a 28-day cycle. The majority of TEAEs at the RP2D were grade 1 or 2. The overall safety profile was consistent across patient dose cohorts and tumor types and consistent with previous fruquintinib studies.The PK profile of fruquintinib in this study is comparable to the PK profile established in studies in China. The dose-normalized exposure parameters between studies in U.S. patients and studies in Chinese patients were generally similar and overlapping, suggesting that the country of origin has no meaningful impact on fruquintinib PK.Anticancer activity was observed in this heavily pretreated population. In the fruquintinib 3 mg dose cohort, the ORR was 16.7% with a DCR of 66.7% and estimated median PFS of 6.9 months. In the fruquintinib 5 mg dose cohort, the ORR was 7.7% with a DCR of 69.2% and estimated median PFS of 5.49 months.