Phase I Clinical Trial of CVL218, a Novel PARP1/2 Inhibitor, in Patients with Advanced Solid Tumors.

CVL218, a novel poly ADP-ribose polymerase (PARP1/2) inhibitor, has strong PARP1/2 selective inhibitory activity and high oral bioavailability. We aimed to assess the safety and tolerability of CVL218 in patients with pretreated advanced solid tumors. Patients in this phase I dose escalation trial received one dose of CVL218 (50, 100, 200, 350, 500, 600, 700, and 850 mg) twice a day. The safety, tolerability, maximum tolerated dose (MTD), dose-limiting toxicity (DLT), recommended dose, as well as antitumor activity of CVL218 were evaluated. A total of 26 patients were enrolled in this trial. The most common treatment-related adverse events were vomiting (76.9%), nausea (76.9%), diarrhea (38.5%), proteinuria (23.1%), and lipase increased (23.1%). DLTs occurred in three patients, one out of six in the 700 mg BID group, and two out of five in the 850 mg BID group, so the MTD was set to 700 mg BID. Overall, the disease control rate (DCR) was 70.8%, while the DCR of patients with high-level doses (≥700 mg BID) and recommended dose (700 mg BID) were both 100%. CVL218 was generally well tolerated and safe. It showed potential antitumor activity in patients treated with the recommended dose.