Multicenter phase 2 trial of second-line onvansertib plus chemotherapy and bevacizumab for KRAS-mutant metastatic colorectal cancer

A multicenter phase 2 trial in the US evaluated the PLK1 inhibitor onvansertib in combination with FOLFIRI and bevacizumab as second-line treatment for KRAS-mutant metastatic colorectal cancer (mCRC) after first-line oxaliplatin and fluorouracil with or without bevacizumab. Among 53 patients treated, the confirmed objective response rate was 26.4% (95% CI 15.3-40.3) and the median duration of response was 11.7 months (9.4-NR). Grade 3 or 4 adverse events were reported in 62% of patients. Post-hoc analysis revealed that patients with no prior bevacizumab treatment had significantly higher ORR and longer PFS compared with patients with prior bevacizumab treatment: ORR 76.9% versus 10.0% (OR 30.0; p<0.001) and median PFS of 14.9 months versus 6.6 months (HR 0.16; p<0.001). The authors conclude that onvansertib in combination with FOLFIRI and bevacizumab showed significant activity as second-line treatment for KRAS-mutant mCRC, particularly in patients with no prior bevacizumab treatment.