Setanaxib/Pembrolizumab Improves Survival in Head and Neck Cancer

In this double-blind, randomized phase 2 trial (NCT05323656), patients were randomly assigned to receive setanaxib at 800 mg twice daily or matched placebo in combination with pembrolizumab at 200 mg intravenously every 3 weeks.

Combining the investigational NOX enzyme inhibitor setanaxib with pembrolizumab (Keytruda) yielded statistically significant progression-free survival (PFS) and overall survival (OS) improvements compared with pembrolizumab alone in a small cohort of patients with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN), according to a press release on findings from a phase 2 trial (NCT05323656).¹

Among 55 evaluable patients, the median PFS was 5.0 months with setanaxib plus pembrolizumab vs 2.9 months with pembrolizumab plus placebo (HR, 0.58). In each respective treatment arm, the OS rate was 92% vs 68% at 6 months and 88% vs 58% at 9 months (HR, 0.45).

Regarding disease control rate (DCR), 70% of those who received setanaxib/pembrolizumab had a best response of at least stable disease compared with 52% of patients who were treated with pembrolizumab plus placebo. Investigators highlighted no significant difference in the primary end point of best percentage change in tumor size from baseline between the treatment arms.

Data highlighted a statistically significant increase in CD8-positive T cells in tumor tissue among patients in the setanaxib arm, which reflected a boost in tumor immunological activity comparable with prior reports of the agent’s mechanism of action. Treatment with setanaxib plus pembrolizumab appeared to be tolerable, and investigators reported no new safety signals.

“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,” trial investigator Kevin Harrington, BSc, MBBS, MRCP, FRCR, FRCP, PhD, DIC, a professor in Biological Cancer Therapies at The Institute of Cancer Research (ICR) London, and a consultant clinical oncologist at The Royal Marsden NHS Foundation, London, said in the press release.¹

In this double-blind, randomized phase 2 trial, patients were randomly assigned to receive setanaxib at 800 mg twice daily or matched placebo in combination with pembrolizumab at 200 mg intravenously every 3 weeks. The full dataset of the trial will include patients who receive study treatment for at least 15 weeks.

The trial’s primary end point is the best percentage change in tumor size according to RECIST v1.1 criteria.² Secondary end points include PFS, overall response rate, DCR, OS, safety, and PD-L1 expression in tumor tissue.

Patients 18 years and older with histologically or cytologically confirmed SCCHN that is recurrent or metastatic or has no nodal involvement were eligible for enrollment on the trial. Additional eligibility criteria included having measurable disease per RECIST v1.1 guidelines, a life expectancy of at least 6 months, a combined positive score of 1 or higher based on tumor biopsy, an ECOG performance status of 0 or 1, and adequate organ and bone marrow function.

Those with prior treatment with pembrolizumab, known active central nervous system metastases and/or carcinomatous meningitis, or active autoimmune disease that needed to be managed with systemic therapy within 3 months prior to entry were not eligible for enrollment on the trial. Having an active infection requiring systemic therapy was also grounds for exclusion from the trial.

“This is a very exciting result [that] 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,” Renée Aguiar-Lucander, chief executive officer at Calliditas Therapeutics, the developers of setanaxib, said in the press release.¹ “It is exciting that we now have positive clinical evidence in support of our first in class NOX platform.”

References

1. Calliditas announces positive topline results of Phase 2 head and neck cancer trial with lead NOX inhibitor candidate, setanaxib. News release. Calliditas Therapeutics AB. May 6, 2024. Accessed May 8, 2024.
2. A study of setanaxib co-administered with pembrolizumab in patients with recurrent or metastatic squamous cell carcinoma of head and neck (SCCHN). ClinicalTrials.gov. Accessed May 8, 2024. https://tinyurl.com/mrcp2hud