Calliditas Therapeutics AB 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 (SCCHN). The analysis showed statistically significant improvements in progression-free survival (PFS), as well as in overall survival (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 (a standard treatment regimen for SCCHN) 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 (Cancer Associated Fibroblasts). A tumor biopsy was taken prior to randomization and then again after at least 9 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, (PFS median 5 months versus 2.9 months; Hazard ratio= 0.58) and statistically significant improvement in overall survival (OS at 6 months 92% vs 68%; OS at 9 months 88% vs 58%; Hazard ratio=0.45) 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 (primary biliary cholangitis) in third quarter of 2024 and is expecting the investigator led Phase 2 trial in IPF (idiopathic pulmonary fibrosis) to provide top line data in fourth quarter 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 First Half of 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. Worldwide, head and neck cancer accounts for approximately 900,000 cases and over 400,000 deaths annually.

In the United States, head and neck cancer accounts for approximately 71,100 cases annually and 16,100 deaths. In Europe, there were approximately 250,000 cases (an estimated 4% of the cancer incidence) and 63,500 deaths in 2012. Males are affected significantly more than females, with a ratio ranging from 2:1 to 4:1. as per UpToDate.

Recurrence of head and neck cancer, especially in advanced stages is common (50%+), with limited treatment alternatives.