The Q1 2026 CRDF-004 trial update is expected to provide more mature data on onvansertib's efficacy, particularly regarding Duration of Response (DoR) and Progression-Free Survival (PFS), which will significantly influence its accelerated approval pathway for first-line RAS-mutated metastatic colorectal cancer (mCRC).1
Cardiff Oncology's onvansertib, a PLK1 inhibitor, is being evaluated in the Phase 2 CRDF-004 trial in combination with standard-of-care (SoC) FOLFIRI and bevacizumab or FOLFOX and bevacizumab.2 The FDA has previously indicated that an interim endpoint of Objective Response Rate (ORR) with DoR from a seamless trial (CRDF-004 leading to CRDF-005) is acceptable for pursuing accelerated approval.2 Full approval would then be contingent on PFS and a trend in Overall Survival (OS).2
Previous data from the CRDF-004 trial, as of a July 8, 2025 data cut-off, showed promising results. The 30mg onvansertib dose arm demonstrated a 49% confirmed ORR compared to 30% in the control arm, representing a 19% improvement in the intent-to-treat population (N=110).1 Additionally, early PFS data indicated a trend favoring the 30mg onvansertib arm, and the drug continued to be well-tolerated.1
The Q1 2026 update will be critical for several reasons:
- Confirmation of Efficacy: More mature data on DoR and PFS will either reinforce or challenge the earlier positive signals. Strong, sustained DoR and a statistically significant improvement in PFS would bolster the case for accelerated approval.1
- FDA Discussions: Positive and robust data from this update will facilitate discussions with the FDA regarding the protocol for the registrational Phase 3 CRDF-005 trial, which is planned to follow CRDF-004.1
- Risk Mitigation: Conversely, if the update reveals a less favorable profile for DoR or PFS, it could introduce delays or require additional data, potentially impacting the timeline for accelerated approval and subsequent registrational studies.
In essence, the Q1 2026 update is a key milestone that will provide the more mature data necessary to further solidify onvansertib's path toward accelerated approval, particularly by demonstrating a durable response and progression-free survival benefit.
