Calliditas Therapeutics AB has announced interim data from its proof-of-concept phase 2 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.
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 tumor size and PFS related results. Twelve patients had tumor 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.
Pathways impacted
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 programs.
Pathology analysis showed preliminary evidence of an increase in immunological activity within tumors of patients treated with setanaxib, with favorable changes in Foxp3and PDL-1 CPS. As SMA levels at baseline were not balanced between the groups, and tumor 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.
“Based on the encouraging clinical and transcriptomic results, data clearly support the continuation of the trial, which will read out on tumor 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 programs. 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.
Calliditas Therapeutics‘ trial details
The trial is a randomized, placebo-controlled, double-blind, proof-of-concept phase 2 study investigating the effect of setanaxib 800 mg 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 tumors.
A tumor biopsy is taken prior to randomization and then again after at least nine weeks of treatment. Treatment will continue until unacceptable toxicity or tumor progression. The study is expected to read out final data in 2024.
Earlier this year, Calliditas Therapeutics announced positive topline results from its global, randomized, double-blind, placebo-controlled phase 3 clinical trial investigating the effect of Nefecon (TARPEYO/Kinpeygo (budesonide) delayed release capsules) versus placebo in patients with primary IgA nephropathy.