Supportive interim data from Phase II head and neck cancer trial 

Calliditas Therapeutics has announced interim data from a proof-of-concept Phase II trial in patients with squamous cell carcinoma of the head and neck (SCCHN) with its lead NOX 1 and 4 inhibitor product candidate, setanaxib.   

The analysis reflects encouraging early clinical progression-free survival (PFS) results and is supportive of the presumed anti fibrotic mode of action of setanaxib.  

Patient data analysis 

The basis for the analysis consisted of a data set of 20 patients with recurrent or metastatic SCCHN, out of which 16 patients had evaluable tumour size and PFS related results. Twelve patients had tumour biopsies before and after treatment that were evaluable for the biomarker analysis, which included transcriptomic analysis and also evaluated pathology markers such as SMA, Foxp3 regulatory T cells and PDL-1 CPS. Due to the small sample size and heterogeneity of the patient population, any inferences from the interim analysis should be treated with caution.  

Transcriptomic analysis  

The transcriptomic analysis showed that the two top pathways impacted by the treatment were fibrosis‑related signaling pathways (the Idiopathic Pulmonary Fibrosis Signaling Pathway and Hepatic Fibrosis/Hepatic Stellate Cell Activation Pathway), providing support for the presumed mode of action relating to modulation of activated (myofibroblastic) fibroblasts, as well as the ongoing clinical programmes.  

Pathology analysis  

Pathology analysis showed preliminary evidence of an increase in immunological activity within tumours of patients treated with setanaxib, with favourable changes in Foxp3and PDL-1 CPS. As SMA levels at baseline were not balanced between the groups, and tumour biopsy samples were generally small, it was not possible to draw any conclusions regarding setanaxib’s impact on SMA reduction.  

In terms of PFS, seven out of the 16 evaluable patients were progression-free with either stable disease or partial response, out of which six were in the setanaxib arm and one was in the placebo arm. Six of the seven patients were still on the study drug at the time of the data read out with the longest period on drug being reported as 21 weeks, related to a patient in the setanaxib arm.  

The clinical trial  

The trial is a randomised, placebo-controlled, double-blind, proof-of-concept Phase II study investigating the effect of setanaxib 800mg twice daily in conjunction with pembrolizumab 200mg IV, administered every three weeks (an accepted standard treatment regimen for SCCHN), in at least 50 patients with moderate or high CAF-density tumours.  A tumour biopsy is taken prior to randomisation and then again after at least nine weeks of treatment. Treatment will continue until unacceptable toxicity or tumour progression, as is typical for oncology trials. The study is expected to read out final data in 2024. 

Official comments 

“Based on the encouraging clinical and transcriptomic results, data clearly support the continuation of the trial, which will read out on tumour size and progression free survival in the full trial population next year. Also, it is interesting that the transcriptomic results clearly pointed to beneficial impact on two fibrosis‑related signaling pathways, supporting the presumed mode of action as well as our pipeline programmes. We are excited about the potential of setanaxib in disease areas where today treatment options are limited,” said CEO Renée Aguiar-Lucander. 

“We are pleased with these encouraging interim data in a patient population where additional effective treatments are needed, and look forward to completing the study in collaboration with our excellent sites and investigators,” said CMO Richard Philipson. 

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