Trial results for a Phase 2 study investigating setanaxib co-administered with pembrolizumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) were posted on ClinicalTrials.gov on 2025-05-09. The study showed a median progression-free survival of 151 days for the combination therapy, compared to 87 days for pembrolizumab with placebo.
Background
The study aimed to compare the change in tumor size per Response Evaluation Criteria in Solid Tumours Version 1.1 (RECIST v1.1) in patients with recurrent or metastatic SCCHN treated with setanaxib and pembrolizumab versus those treated with placebo and pembrolizumab.
Trial design
The study (NCT05323656) was a Phase 2, randomized trial that enrolled 55 participants with recurrent or metastatic squamous cell carcinoma of the head and neck. Participants received either setanaxib 1600 mg and pembrolizumab 200 mg or placebo and pembrolizumab 200 mg. The primary objective, as stated in the study summary, was to compare the change in tumor size per RECIST v1.1 between the treatment groups.
Key results
The trial reported several key measurements and analyses:
- Best Percentage Change in Tumour Size:
- For the setanaxib 1600 mg and pembrolizumab 200 mg group, the least squares mean change was -7.88% (Standard Error: 9.323).
- For the placebo and pembrolizumab 200 mg group, the least squares mean change was -12.93% (Standard Error: 8.977).
An ANCOVA analysis showed a LS Mean Difference of 5.05 (80.0% CI: -11.98 to 22.0) with a p-value of 0.7008.
- Progression Free Survival (PFS):
- The median PFS for the setanaxib 1600 mg and pembrolizumab 200 mg group was 151 days.
- The median PFS for the placebo and pembrolizumab 200 mg group was 87 days.
A Cox Regression analysis yielded a Hazard Ratio (HR) of 0.58 (80.0% CI: 0.38 to 0.89) with a p-value of 0.1023. Another Hazard Ratio of 0.448 (80.0% CI: 0.24 to 0.85) was also reported without a formal test of significance.
- Change From Baseline in Cancer-associated Fibroblasts (CAFs) Level in Tumour Tissue:
- For the setanaxib 1600 mg and pembrolizumab 200 mg group, the mean change was 58.13% positivity of tumour stromal component (Standard Deviation: 37.006). A second measurement showed a mean change of 50.50% positivity of tumour stromal component (Standard Deviation: 31.023).
- For the placebo and pembrolizumab 200 mg group, the mean change was 52.00% positivity of tumour stromal component (Standard Deviation: 23.357). A second measurement showed a mean change of 36.50% positivity of tumour stromal component (Standard Deviation: 30.373).
An ANCOVA analysis showed a LS Mean Difference of 9.5 (80.0% CI: -2.3 to 21.3) with a p-value of 0.2986.
- Change From Baseline in the Number of Cluster of Differentiation 8 (CD8+) Tumour Infiltrating Lymphocytes (TILs) in Tumour Tissue:
- For the setanaxib 1600 mg and pembrolizumab 200 mg group, the mean change was 18.13 cells/High Power Field (HPF) (Standard Deviation: 8.901). A second measurement showed a mean change of 41.14 cells/High Power Field (HPF) (Standard Deviation: 34.535).
- For the placebo and pembrolizumab 200 mg group, the mean change was 21.34 cells/High Power Field (HPF) (Standard Deviation: 19.789). A second measurement showed a mean change of 38.30 cells/High Power Field (HPF) (Standard Deviation: 26.553).
An ANCOVA analysis showed a LS Mean Difference of 6.83 (80.0% CI: -9.86 to 23.52) with a p-value of 0.5918.
What this means
The results suggest a potential benefit in progression-free survival for the combination of setanaxib and pembrolizumab in recurrent or metastatic SCCHN, with a median PFS of 151 days compared to 87 days for pembrolizumab with placebo. The observed Hazard Ratio of 0.58 for PFS, while not meeting conventional statistical significance (p-value 0.1023), indicates a directional reduction in the risk of progression. However, the combination did not show an improved best percentage change in tumor size compared to pembrolizumab with placebo. Further research may be warranted to explore the PFS findings and the role of setanaxib in this patient population.
Source
The trial results were sourced from ClinicalTrials.gov, a public registry of clinical studies. The data for study NCT05323656, titled "A Study of Setanaxib Co-Administered With Pembrolizumab in Patients With Recurrent or Metastatic Squamous Cell Carcinoma of Head and Neck (S," was posted on 2025-05-09 on clinicaltrials.gov.