Cardiff Oncology Publishes Phase 2 KRAS Mutant mCRC Trial Data in Journal of Clinical Oncology

Cardiff Oncology, Inc., a biotechnology company in the clinical stage of development, has recently shared promising results from its Phase 2 trial, which investigated the efficacy of onvansertib in combination with FOLFIRI and bevacizumab (bev) for treating KRAS mutant metastatic colorectal cancer (mCRC). The findings have been published in the Journal of Clinical Oncology, highlighting the notable clinical activity and tolerance of this combination therapy, particularly in bev-naïve patients.

The study revealed that the addition of onvansertib to the standard treatment regimen resulted in a significant increase in the objective response rate (ORR) among patients who had not previously been treated with bev. Specifically, the ORR in bev-naïve patients was 77%, a stark contrast to the 10% observed in patients who had been exposed to bev. Additionally, the median progression-free survival (mPFS) was substantially higher in the bev-naïve group, reaching 14.9 months compared to just 6.6 months in the bev-exposed group.

Heinz-Josef Lenz, MD, a Professor of Medicine and Deputy Cancer Center Director at USC Norris Comprehensive Cancer Center, and the national principal investigator of the trial, expressed excitement over these findings. He emphasized the importance of developing new and effective treatments for KRAS mutant mCRC, a condition that has seen limited advancements over the years. Dr. Lenz highlighted the remarkable 77% ORR in bev-naïve patients and looked forward to exploring the potential of onvansertib in the first-line setting.

Dr. Fairooz Kabbinavar, Chief Medical Officer of Cardiff Oncology, echoed this sentiment, stating pride in the recognition from such a prestigious oncology journal. Dr. Kabbinavar noted the groundbreaking nature of the clinical and preclinical findings, which demonstrated a 7.7-fold increase in ORR in bev-naïve patients. This success is attributed to a novel mechanism of action of onvansertib, which was discovered through translational work. The FDA's support and the promising results led Cardiff Oncology to initiate a Phase 2 randomized clinical trial (CRDF-004), examining onvansertib in combination with FOLFIRI and bev or FOLFOX and bev as a first-line treatment for patients with RAS mutant mCRC. The company aims to release initial data from this trial in the second half of 2024.

The published data from the Phase 2 trial (NCT03829410) provide a comprehensive look at the effectiveness and tolerance of onvansertib when combined with FOLFIRI and bev. In preclinical models, onvansertib showed a significant inhibitory effect on the hypoxia pathway and exhibited robust antitumor activity by inhibiting angiogenesis when combined with bev. These findings lay the groundwork for the ongoing CRDF-004 trial and underscore the potential of onvansertib as a valuable addition to the current treatment options for KRAS mutant mCRC.

Cardiff Oncology’s broader development strategy focuses on leveraging PLK1 inhibition, an established oncology drug target, to develop novel therapies across various cancers. Onvansertib, their lead asset, is being evaluated in combination with standard care therapies in several clinical programs targeting RAS-mutated mCRC, metastatic pancreatic ductal adenocarcinoma (mPDAC), small cell lung cancer (SCLC), and triple-negative breast cancer (TNBC). These endeavors aim to address tumor vulnerabilities and overcome treatment resistance, potentially offering superior clinical benefits compared to standard care alone.

The promising results from the Phase 2 trial and the ongoing efforts in the CRDF-004 trial highlight Cardiff Oncology's commitment to advancing cancer treatment and improving patient outcomes. With the anticipated release of initial data from the first-line RAS-mutant mCRC CRDF-004 trial in the latter half of 2024, the oncology community eagerly awaits further insights into the potential of onvansertib in providing effective treatment options for patients with this challenging cancer type.