Cardiff Oncology has shared updated results from its phase 2 colorectal cancer trial, revealing that the study drug has yet to reach the median progression-free survival (PFS) as the biotech prepares to enter pivotal development.
The trial is evaluating onvansertib, Cardiff’s oral PLK1 inhibitor, in first-line RAS-mutated metastatic colorectal cancer. Patients received the study drug with FOLFIRI or FOLFOX, standard-of-care chemotherapy regimens, and the angiogenesis inhibitor bevacizumab. An earlier cut of the data linked the addition of the higher, 30 mg dose of onvansertib to FOLFIRI/bev to an improved response rate.
On Tuesday, Cardiff presented updated data at the American Society of Clinical Oncology annual meeting. The presentation reiterated parts of the earlier update, such as the 72.2% response rate on high-dose onvansertib and FOLFIRI/bev and the 42.1% response rate in the comparable control cohort.
Responses on onvansertib were deeper and more durable, Cardiff said. The 30 mg arm has yet to reach median PFS. Cardiff previously reported a median PFS of 10.9 months on FOLFIRI/bev and in the wider control cohort that included FOLFOX/bev patients.
Related
Longer PFS on 30 mg of onvansertib translated into hazard ratios of 0.55 and 0.57 versus FOLFIRI/bev, depending on whether progression was assessed by blinded independent central review or investigators. A lower hazard ratio indicates a bigger benefit of the treatment. Cardiff reported a hazard ratio of 0.38, with narrower confidence intervals, in the earlier cut of the data.
After talking with two gastrointestinal cancer experts in October, TD Cowen analysts said in a note to investors that physicians were looking for onvansertib to have about a four-month median PFS benefit.
Cardiff is moving the 30 mg dose of onvansertib with FOLFIRI/bev into phase 3. As the biotech revealed in earlier updates, adding onvansertib to FOLFOX/bev provided no meaningful benefits and the combination won’t be taken into late-stage development.
William Blair analysts went into the ASCO presentation wanting “a biologically plausible explanation” for the differences in efficacy between the two chemotherapy regimens. Onvansertib’s failure to add to FOLFOX/bev’s efficacy may have commercial implications, with the analysts estimating in a note to investors that U.S. physicians use FOLFIRI/bev in about 30% of frontline patients.
Related
Limiting onvansertib to the subset of patients “could pose an adoption headwind, pending future clinical and regulatory success,” the analysts said. They noted skepticism about onvansertib’s potential and acknowledged that Cardiff “will likely seek dilutive funding or partnership opportunities to fund the pivotal study for onvansertib.”
Cardiff ended March with $46.1 million in cash, equivalents and short-term investments, a sum that it predicted will fund operations into the first quarter of 2027. The biotech’s share price, which crashed after it published onvansertib data and made leadership changes in January, closed at $1.48 on Monday.
