Calliditas setanaxib trial misses primary endpoint, meets secondary endpoints

Calliditas Therapeutics announced data from the proof-of-concept Phase 2 trial evaluating setanaxib, its lead NOX enzyme inhibitor, in combination with pembrolizumab, in patients with squamous cell carcinoma of the head and neck, or SCCHN. The analysis showed statistically significant improvements in progression-free survival, or PFS, as well as in overall survival, or OS, with statistically significant changes in tumor biology consistent with the mechanism of action of setanaxib. The trial is a randomized, placebo-controlled, double-blind Phase 2 study investigating the effect of setanaxib 800mg twice daily in conjunction with pembrolizumab 200mg IV, administered every 3 weeks with the full dataset reflecting all patients having had the opportunity to complete at least 15 weeks of treatment. The basis for the analysis consisted of a dataset of 55 patients with recurrent or metastatic SCCHN and moderate or high CAF-density tumors. A tumor biopsy was taken prior to randomization and then again after at least nine weeks of treatment. The treatment groups were well-balanced with no clinically relevant differences between the groups observed at baseline. Patients treated with pembrolizumab and setanaxib showed statistically significant improvements in key secondary endpoints, such as progression-free survival, and statistically significant improvement in overall survival compared to patients treated with pembrolizumab and placebo. There was also an improvement in disease-control rate in setanaxib-treated patients, with 70% in the setanaxib arm showing a best response of at least stable disease compared to 52% in the placebo arm. No significant difference in the primary endpoint of best percentage change from baseline in tumor size was observed. Transcriptomic analysis of tumor biopsy samples showed a statistically significant increase in CD8+ T-cells in tumor tissue from patients treated with setanaxib, indicating an increase in tumor immunological activity consistent with the mechanism of action of setanaxib. The tolerability of setanaxib when given with pembrolizumab was generally good, with no new safety signals identified. The company is conducting additional clinical trials with setanaxib and will read out its Phase 2 trial in PBC in Q3 of 2024 and is expecting the investigator led Phase 2 trial in IPF to provide top line data in Q4 of 2024, subject to recruitment. There is also an ongoing Phase 2 proof of concept trial in Alport syndrome, which is expected to deliver top line data in 1H, 2025. The company plans to arrange an R&D day in Stockholm later this month to provide additional details regarding the Phase 2 trial and other data supporting the mechanism of action of setanaxib. Further details will be provided by way of a press release.