Recently, Cardiff Oncology announced positive data from its phase 2 CRDF-004 study, which evaluated the use of its PKL1 inhibitor in combination with the current standard of care (SOC) to treat 1st-line RAS-mutated metastatic colorectal cancer (mCRC) patients. By SOC I mean that typically this group of patients either receives FOLFIRI + AVASTIN (bevacizumab) or FOLFOX + AVASTIN to treat their disease. The goal was to test out both doses of 20 mg and 30 mg of onvasnertib with either of these combinations to see if adding it would have a more profound effect compared to SOC doublet alone. The highest dose tested achieved the maximum result, in that patients who took 30 mg of this drug with SOC achieved a confirmed objective response rate (ORR) of 49%.
The reason why this data point is critical is because patients who took SOC only achieved an ORR of 30%. The point is that those who took the onvansertib combination ended up with a 19% better ORR. This is one side of the data, though, because what has not yet been fully revealed would be the progression-free survival (PFS) number. However, this makes sense, as it is too early to actually state what this is because patients have only reached a median follow-up time of only 6 months. With that being said, despite the short time frame and the median PFS not being reached, there appears to be a separation shown between the patients who took 30 mg onvansertib + SOC, compared to SOC alone.
This data didn’t cause the share price to trade higher, but what it might do is gain an audience with the FDA. That is, it hopes to meet with the FDA based on this revealed data and see if it can gain favor to begin the phase 3 CRDF-005 trial. If given the go-ahead to start this late-stage study, it will be a crucial turning point for it because it is being designed for two pathways towards approval. By that I mean there is the possible incorporation of ORR as being used for Accelerated Approval (if the FDA agrees to this upon the end of the meeting) and then PFS for full confirmatory FDA approval. Either way, the initiation of CRDF-005 brings Cardiff one step closer to getting this therapy towards the finish line of potentially receiving U.S. market approval for it to target these 1st-line RAS-mutated mCRC patients.
The beauty of its PLK1 inhibitor is that it is not like the other approved drugs that target RAS-mutant cancer patients, where only a subset of patients are targeted. For instance, you have FDA-approved KRAS G12C inhibitors like LUMAKRAS (SOTORASIB) from Amgen and KRAZATI (ADAGRASIB) from Bristol-Myers Squibb. Both of these drugs have been approved to target non-small cell lung cancer (NSCLC) and colorectal cancer (CRC) patients with the KRAS G12C mutation. These work well for a subset of these patients with these specific tumor types. Consider that in colorectal cancer, it is believed that about 3% to 4% of these patients carry the KRAS G12C mutation.
The point here is that Cardiff, with onvansertib, as a PLK1 inhibitor, is able to target a larger slice of the pie of CRC patients. It is able to go after 52% of them with an RAS mutation. The ability to use this drug in a broader fashion is what makes it that much more appealing, because it is not confined to a smaller percentage of RAS-mutant solid tumors. Investors are not left without hope because there is another milestone pertaining to the development of onvansertib for the treatment of these patients with 1st-line RAS-mutated mCRC, which is a program update in Q1 of 2026. This is likely to make another huge inflection point for further advancement of this program.
The science of onvansertib as a PLK1 inhibitor is ideal. The thing is that PLK1 is an enzyme that is overexpressed in a variety of tumor cells. Specifically, these tumor cells use this enzyme in the “M” phase of the cell cycle (mitosis phase where cells are dysregulated and just grow in an out-of-control fashion). This uncontrolled growth is what allows tumors to grow and spread in the patient’s body. Beyond this, PLK1 has another job, which is to act as a repair function for damaged DNA of cells in the “S” phase of the cell cycle (the DNA replicating phase where daughter cells receive a full set of chromosomes during cell division). This is where the addition of SOC chemotherapies comes into play in that they work, but the damage they cause ignites the tumor’s ability to repair damaged DNA with the PLK1 enzyme. With onvansertib being a PLK1 inhibitor, it blocks this action of DNA repair. and in turn causes an increase in the efficacy of SOC treatment.
The thing is that onvansertib is versatile, as it is not just confined to one specific tumor type. With that being said, the company also reported positive data from an investigator-initiated trial using onvansertib in combination with paclitaxel to treat patients with metastatic triple-negative breast cancer (mTNBC). There were positive signals noted here, as presented at the most recent American Society of Clinical Oncology (ASCO) 2025 medical conference from this phase 1b study. It was noted there was a 40% ORR achieved, which is broken down into two confirmed partial responses (PRs) and two unconfirmed PRs.
This is another avenue of its pipeline it could explore, considering this data is good enough to explore in a larger pool of patients. However, it is going to need to use its cash wisely, as it ended the most recent Q2 of 2025, ending June 30, 2025, with $71 million in cash. It believes that this should be enough to fund itself into Q1 of 2027. The good news is that the program dealing with onvansertib plus SOC targeting 1st-line RAS-mutated mCRC patients is being done in collaboration with Pfizer.