Calliditas puts a brave face on setanaxib failure
A phase 2 head and neck trial missed its primary endpoint, but the group is taking heart from survival data.
A phase 2 head and neck trial missed its primary endpoint, but the group is taking heart from survival data.
Calliditas’s NOX1/4 inhibitor setanaxib, gained through the €32m purchase of Genkyotex, looked like a long shot even before the company reported the failure of its phase 2 trial in head and neck cancer this week.
However, the miss wasn’t immediately apparent from Calliditas’s press release, with the group focusing on improvements in both PFS and OS with setanaxib and Keytruda, versus Keytruda alone. These data do indeed show a hint of promise, but with few details to go on at present there are many reasons to be cautious.
Primary endpoint miss
The first is that the study, in 55 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), flunked its primary endpoint of best percentage change from baseline in tumour size.
Calliditas didn’t give any numbers here, except to say there was no significant difference between the two groups. But the company did disclose median progression-free survival data, as well as landmark overall survival results at six and nine months.
And here Calliditas claimed "statistically significant improvements"; it's not apparent how the group can make this claim, or how any statistics can be gleaned from survival endpoints, given that the primary was missed, using up all or most of the trial's statistical powering. It's likely that the PFS and OS findings are purely exploratory.
That said, the PFS data in particular do look promising when stacked up against results seen in head and neck studies of checkpoint inhibitors.
Cross-trial comparison in second-line head and neck cancer
| Calliditas ph2 (NCT05323656) | Keynote-040 (NCT02252042)* | Checkmate-141 (NCT05323656)^ | ||
|---|---|---|---|---|
| Setanaxib + Keytruda | Keytruda | Keytruda | Opdivo | |
| Median PFS (months) | 5.0 | 2.9 | 2.1 | 2.0 |
| Median OS (months) | N/A | N/A | 8.4 | 7.5 |
| OS at 6 months | 92% | 68% | N/A | N/A |
| OS at 9 months | 88% | 58% | N/A | N/A |
| OS at 12 months | N/A | N/A | 37% | 36% |
Notes: *potentially confirmatory trial, which failed its OS primary endpoint; ^basis for full approval of Opdivo in 2L SCCHN.
The lack of detail given by Calliditas provides plenty of additional caveats, including that the survival data are difficult to interpret without seeing the Kaplan-Meier curves, with no information about patient censoring. There's no detail on baseline characteristics, and it's also unclear how many of the 55 patients were included in the analyses.
Ultimately, with the OS data clearly immature, and more information needed to gauge the maturity of the PFS data, Calliditas still has a lot to prove before setanaxib can be considered a contender. Perhaps the primary endpoint miss can be overlooked if the survival data are robust – but this is still an open question.
At the time of publishing Calliditas hadn't responded to a request from ApexOnco to clarify the data.
More details
The company is planning an R&D day later this month, and this will include more details on the phase 2 trial. Calliditas hasn’t yet outlined its next steps for setanaxib in cancer, but has previously said it’s looking for a partner here.
The main focus for the project seems to lie outside oncology, but earlier data from Genkyotex here were unconvincing. Others haven’t rushed into this space either, with setanaxib the only NOX inhibitor in development for cancer, according to OncologyPipeline.
At least Calliditas’s didn’t pay much for Genkyotex, but it is still far too early to call setanaxib, or the deal, a success.
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