Cardiff Oncology (CRDF) Stifel 2025 Healthcare Conference summary

Key clinical insights

• Onvansertib, a selective PLK1 inhibitor, is being evaluated in first-line RAS-mutated metastatic colorectal cancer, targeting a broad patient population due to its mutation-agnostic mechanism.

• The ongoing CARDIF-004 trial compares standard of care with and without onvansertib at two dose levels, focusing on dose selection for future registrational studies.

• Interim data show higher confirmed objective response rates with onvansertib (up to 49%) versus control (30%), with deeper and faster tumor shrinkage, especially at the 30 mg dose.

• Safety profile remains favorable, with no incremental increase in neutropenia or other toxicities compared to control.

• Early progression-free survival data are encouraging, and the 30 mg dose will advance to a seamless phase 3 trial for both accelerated and full approval.

Scientific rationale and translational findings

• Preclinical and clinical data suggest synergy between onvansertib and bevacizumab, particularly in BEV-naive patients, leading to improved tumor shrinkage and progression-free survival.

• Onvansertib inhibits HIF-1 alpha, blocking tumor adaptation to hypoxia and angiogenesis, complementing bevacizumab's VEGF inhibition.

• These findings have resulted in new intellectual property, with patents extending into at least 2043 for colorectal cancer.

Regulatory and development strategy

• The FDA recommended pivoting from second-line to first-line development based on strong early data, and a seamless phase 3 trial design is planned to support both accelerated and full approval.

• The registrational trial will use response-based endpoints for accelerated approval and progression-free survival for full approval, with design informed by recent regulatory precedents.

• Next data readout with approximately 12 months median follow-up is expected in Q1 next year, with disclosure planned via a company-sponsored event for flexibility.