As advancements in cancer treatment continue to evolve, the pursuit of more effective therapies for metastatic colorectal cancer remains a critical focus in the pharmaceutical industry. Cardiff Oncology, Inc. (NASDAQ:CRDF) on Tuesday released data from the ongoing CRDF-004 Phase 2 clinical trial evaluating onvansertib in combination with standard-of-care (SoC) in patients with first-line RAS-mutated metastatic colorectal cancer (mCRC).
Patients were randomized to one of six arms, including 20mg of onvansertib plus SoC, 30mg of onvansertib plus SoC, or SoC alone.
The overall objective response rate (ORR) was 59% on the high dose and 50% in the 20 mg dose, compared to a 43% response rate in the control arm.
After removing the ORRs at 6 months, the confirmed ORRs for the high-dose, low-dose, and control arms were 49%, 42%, and 30%, respectively.
Onvansertib Shows Promise With High Response Rates
For comparison, December 2024 data showed an ORR of 57% in all onvansertib patients, with 50% in the 20mg dose of onvansertib + SoC arm and 64% in the 30mg dose of onvansertib + SoC arm, compared to 33% in the SoC alone arm.
Spider Plots, displaying the change in tumor size from baseline for each patient over time, demonstrate deeper responses in patients receiving the 30mg dose of onvansertib combined with the SoC compared to the control arm and the 20mg dose of onvansertib arm.
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Both the 20mg and 30mg onvansertib arms demonstrated an early separation of the progression-free Survival (PFS) curves compared to the control arm at a median follow-up time of 6 months.
While the median PFS has not been reached, a dose-dependent effect was observed in favor of the 30mg onvansertib dose.
The safety analysis was conducted for the 104 patients dosed in the trial. Onvansertib, in combination with chemotherapy and bevacizumab, was well-tolerated, and no major or unexpected toxicities were observed.
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Grade 3 or higher adverse events were infrequent, with neutropenia being the most common treatment-emergent adverse event associated with onvansertib.
Update on first-line mCRC program expected by the first quarter of 2026.
William Blair believes the current data on onvansertib justifies further investment, including moving forward with a Phase 3 trial.
The overall data shows that onvansertib is clearly effective, which analyst Andy Hsieh says weakens the bearish argument against the stock.
The key question is whether the ORR improvement will result in a meaningful gain in PFS, the main measure needed for approval.
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Looking at past data, even a modest improvement in response rates—like the 11% increase seen in the Phase 3 TRIBE study—can result in a successful outcome in key trials, especially if it also boosts PFS.
In the Phase 3 BREAKWATER study for BRAF-mutated colorectal cancer, a 20% jump in response rate led to meaningful gains in PFS and overall survival.
Analyst Hsieh writes that the current valuation reflects considerable skepticism regarding the compound's clinical profile, which William Blair disagrees with.
William Blair holds a bullish view that onvansertib could potentially disrupt the RAS-mutated frontline mCRC treatment paradigm. Reiterates Outperform rating.
CRDF Price Action: Cardiff Oncology shares were down 19.94% at $2.65 at the time of publication on Wednesday, according to Benzinga Pro data.
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