Cardiff Oncology Presents Novel Preclinical Data at AACR Annual Meeting 2024 that Supports Ongoing First-line RAS-mutated mCRC Clinical Study - Seite 2

Key highlights from the company’s five poster presentations at AACR are below.

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 HIF1α 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.