Cardiff Oncology, Inc. announced the presentation of five abstracts at the American Association for Cancer Research (AACR), taking place from April 5-10, 2024, in San Diego, California. In combination, the abstracts underscore the significant potential of the company?s lead molecule onvansertib in metastatic colorectal cancer (mCRC) and other cancers. A Phase 1b/2 Clinical Study of Onvansertib in Combination with FOLFIRI/Bev Revealed a New Role of PLK1 in regulating the Hypoxia Pathway in KRAS-mutated Metastatic Colorectal Cancer: Bev naïve patients treated with onvansertib + FOLFIRI/bev demonstrated a significantly greater overall response rate [odds ratio=13.64, p<0.001] and longer PFS [hazard ratio=0.21, p=0.003] compared to bev exposed patients.

Onvansertib reduced tumor vascularization as a single agent and onvansertib + bev combination resulted in a greater decrease in tumor vascularization. In vitro, onvansertib inhibited the activation of the hypoxia pathway through the regulation of the transcription factor HIF1a and its downstream targets. Collectively the updated clinical and preclinical data further support the ongoing CRDF-004, Phase 2 trial of onvansertib + chemo/bev for the first-line treatment of RAS-mutated mCRC patients, who by definition are bev naïve.

A Phase 2, Randomized, Open-label Study of Onvansertib in Combination with Standard-of-Care (SoC) Versus SoC Alone for First-line Treatment of RAS-mutated Metastatic Colorectal Cancer: CRDF-004 is a Phase 2 randomized trial generating preliminary safety and efficacy data and evaluating two different doses of onvansertib to confirm an optimal dose. Onvansertib will be added to standard-of-care consisting of FOLFIRI plus bev, or FOLFOX plus bev. A total of 90 patients will be randomized in a 1:1:1 ratio to either 20mg of onvansertib plus standard-of-care, 30mg of onvansertib plus standard-of-care, or standard-of-care alone.

The primary endpoint of the study includes objective response rate (ORR), and the key secondary endpoints include progression-free survival (PFS) and duration of response (DoR). The PLK1 Inhibitor Onvansertib is Active as Monotherapy and in Combination with Cetuximab in RAS Wild-type Metastatic Colorectal Cancer Patient-derived Xenografts: Single agent onvansertib successfully induced tumor stasis or regression in 70% (14/20) of the RAS WT mCRC patient-derived xenograft (PDX) models tested. This included both models sensitive to cetuximab (5/7, 71%) and resistant to cetuximab (9/13, 69%).

Onvansertib in combination with cetuximab induced tumor stasis or regression in 90% (18/20) of the models tested. Overall, the antitumor activity of the combination was superior compared to monotherapy with either agent in both cetuximab sensitive and resistant models.