Positive results of Phase II head and neck cancer trial 

Calliditas Therapeutics has announced data from the proof-of-concept Phase II 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 tumour biology consistent with the mechanism of action of setanaxib. 

Trial details, treatment groups 

The trial is a randomised, placebo-controlled, double-blind Phase II study investigating the effect of setanaxib 800mg twice daily in conjunction with pembrolizumab 200mg IV, administered every three 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 tumours (Cancer Associated Fibroblasts). A tumour biopsy was taken prior to randomisation 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 five 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 nine 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 tumour size was observed. Transcriptomic analysis of tumour biopsy samples showed a statistically significant increase in CD8+ T-cells in tumour tissue from patients treated with setanaxib, indicating an increase in tumour 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 II trial in PBC (primary biliary cholangitis) in Q3 of 2024 and is expecting the investigator led Phase II trial in IPF (idiopathic pulmonary fibrosis) to provide top line data in Q4 of 2024, subject to recruitment. There is also an ongoing Phase II proof of concept trial in Alport syndrome, which is expected to deliver top line data in the first half of 2025.   

“It is very encouraging to see statistical significance on important clinical outcomes in this relatively small study, which provides an excellent basis for advancing setanaxib in this hard-to-treat population,” said Kevin Harrington, Professor in Biological Cancer Therapies at The Institute of Cancer Research (ICR) London, Consultant Clinical Oncologist at The Royal Marsden NHS Foundation, London, and Investigator on the trial.

“This is a very exciting result which provides clinical evidence of the mode of action of setanaxib in line with our thesis of its anti-fibrotic effects, and with results beyond our expectations for a study of this size. It is exciting that we now have positive clinical evidence in support of our first in class NOX platform” said CEO Renée Aguiar-Lucander. 

Megan Thomas, Multimedia Editor, DDW

Related Articles

Join FREE today and become a member
of Drug Discovery World

Membership includes:

  • Full access to the website including free and gated premium content in news, articles, business, regulatory, cancer research, intelligence and more.
  • Unlimited App access: current and archived digital issues of DDW magazine with search functionality, special in App only content and links to the latest industry news and information.
  • Weekly e-newsletter, a round-up of the most interesting and pertinent industry news and developments.
  • Whitepapers, eBooks and information from trusted third parties.
Join For Free