Cardiff Oncology (CRDF) Study Result summary

Study Design and Objectives

• The CRDF-004 Phase 2 trial is a randomized study in first-line RAS-mutated mCRC, enrolling 90 patients to compare 20mg and 30mg onvansertib plus standard of care (SoC) versus SoC alone, with arms balanced for baseline characteristics.

• The primary endpoint is objective response rate (ORR); secondary endpoints include duration of response, progression-free survival, and safety, all assessed by blinded independent central review.

• The trial aims to confirm the optimal onvansertib dose for registration, evaluate efficacy and safety, and inform future regulatory strategy.

• Enrollment is progressing well, with two-thirds of patients enrolled and completion expected in early 2025.

• Additional clinical data are expected in the first half of 2025.

Efficacy Results

• The 30mg onvansertib arm achieved a 64% ORR, nearly double the 33% in the SoC control arm, with deeper tumor regressions and more pronounced tumor shrinkage.

• Across all experimental arms, the ORR was 57% versus 33% in controls, with consistent efficacy between FOLFIRI and FOLFOX backbones.

• Dose response was observed: higher onvansertib dose led to deeper and more frequent responses.

• Most patients remain on trial, with deepening responses over time, especially at the 30mg dose.

• All efficacy data were determined by blinded, independent central review as of November 26, 2024.

Safety and Tolerability

• Onvansertib was generally well-tolerated at both 20mg and 30mg doses, with no unmanageable or unexpected toxicities and manageable side effects.

• Treatment-emergent adverse events were common in all arms, with grade ≥3 events in 55.6% of control and 71.4% of experimental arms.

• Most frequent TEAEs included fatigue, nausea, neutrophil count decrease, and diarrhoea; grade 4 neutropenia resolved with treatment delays.

• Onvansertib can be safely combined with both FOLFIRI and FOLFOX chemotherapy backbones.

• Four patients discontinued: two for curative surgery after becoming resectable, two for adverse events attributed to standard therapies, not onvansertib.