Cardiff goes south again

Cardiff Oncology disappointed last year with an update on its PLK-1 inhibitor onvansertib in first-line colorectal cancer, and now it's done it again. The group’s stock closed down 32% on Tuesday after an unsatisfying and cherrypicked data drop that coincided with the departure of its chief executive and chief financial officers.

Cardiff’s interim leader, Mani Mohindru, told an analyst call that the leadership change was “by no means related to any issues” with onvansertib in colorectal cancer, but investors weren’t buying it. The company didn’t provide any slides detailing the latest results, only putting out a press release, which added to the sense that something might be up.

The data came from the phase 2 CRDF-004 trial, which tested two onvansertib doses, combined with Avastin and Folfox/Folfiri chemo, versus Avastin plus chemo in first-line, RAS-mutated colorectal cancer.

Results were first reported in December 2024, and then again last July; at the second update the magnitude of benefit versus control looked to have waned with the addition of more patients.

Folfiri only

Previous disclosures encompassed onvansertib in combination with both Folfox and Folfiri plus Avastin, but this time Cardiff cherrypicked data only for the Folfiri/Avastin combo. 

Mohindru excused this selective disclosure by claiming that results with onvansertib plus Folfox/Avastin “were not as robust or consistent” as in the Folfiri arm. This makes it impossible to ascertain how the dataset has evolved.

With the Folfiri/Avastin combo, meanwhile, ORR by blinded independent central review was 72% and 44% with onvansertib dosed at 30mg and 20mg respectively. This stacked up against a 43% ORR with either Folfiri or Folfox plus Avastin.

With the 20mg dose looking no better than control, it’s no wonder that Cardiff has chosen to take the higher dose forward.

A dose-response trend was also apparent in early progression-free survival data. Medians weren’t reached in the experimental arms, but Cardiff claimed hazard ratios of 0.37 with the 30mg dose, and 0.57 with the 20mg dose, versus either Folfox or Folfiri plus Avastin.

Still, the PFS analysis included investigator-assessed, as well as centrally assessed events. Cardiff cited a “very small” number of centrally assessed events, raising the question of why it chose this time to report PFS data – especially given that another update from this trial is due in the first half.

Pivotal plans

Perhaps the company is hoping to drum up interest from potential partners ahead of its pivotal trial, CRDF-005, which is slated to start this year amid questions around how Cardiff will fund it. The company had $61m in cash at the end of its third quarter, only enough to get it into the first quarter of 2027.

Mohindru would only say that “strategic discussions” were ongoing. Interestingly, Pfizer has right of first access to data, via a November 2021 investment; when asked if there had been any interest from the big pharma, Mohindru replied that Cardiff had shared the CRDF-004 data with Pfizer, and would “continue to share with them and others”.

In the meantime, Cardiff hopes to discuss the pivotal trial design with the FDA this half, after which it will release more details about pivotal trial design. Mohindru did disclose that the comparator arm was expected to encompass both Folfiri and Folfox chemo, plus Avastin, as both of these regimens were routinely used in first-line CRC.

But, with many details to be ironed out, cash running low, and now the executive departures, there are still big questions around Cardiff’s future.