Onvansertib (PLK1 inhibitor) + FOLFIRI/Bev lifts ORR to 72% and improves PFS signal in 1L RAS-mut mCRC

Onvansertib (Onv) is an oral, selective polo-like kinase 1 (PLK1) inhibitor combined here with standard doublet chemotherapy plus bevacizumab (FOLFIRI+Bev or FOLFOX+Bev) in the randomized Phase 2 CRDF-004 trial (NCT06106308) in previously untreated KRAS/NRAS-mutant metastatic colorectal cancer (ITT n=110; data cutoff Jan 22, 2026; median follow-up ~10 months). The strongest activity was in the Onv 30mg + FOLFIRI+Bev arm: BICR ORR 72.2% (13/18) vs 42.1% with FOLFIRI+Bev (8/19) and 43.2% across combined SoC controls (16/37), with confirmed ORR narrowly missing conventional significance vs SoC (p=0.051) but a 6‑month ORR advantage vs FOLFIRI+Bev (55.6% vs 21.1%, p=0.045); median PFS was not reached vs ~11 months for controls, with HR 0.38 vs FOLFIRI+Bev and HR 0.37 vs combined SoC (p=0.048)—directionally better than the typical ~9–10 month PFS historically reported for bevacizumab + oxaliplatin/fluoropyrimidine regimens in 1L mCRC. Grade ≥3 AEs were described as manageable with no unexpected toxicities; neutropenia was the most common grade ≥3 event.