Setanaxib With Pembrolizumab Boosts Survival in Recurrent/Metastatic SCCHN


Early research suggests setanaxib combined with pembrolizumab may be a promising treatment for patients with squamous cell carcinoma of the head and neck.

Head and neck cancer image: ©

Head and neck cancer image: ©

Setanaxib, a NOX1/4 inhibitor, given in combination with pembrolizumab (Keytruda) led to statistically significant improvements in progression-free survival (PFS) and overall survival (OS) when given as a treatment for patients with squamous cell carcinoma of the head and neck (SCCHN), according to findings from a proof-of-concept, phase 2 trial (NCT05323656).1

The PFS rates between those given the combination of setanaxib and pembrolizumab vs placebo and pembrolizumab was 5 months vs 2.9 months (HR, 0.58), and the OS rates were 92% vs 68% at 6 months and 88% vs 58% at 9 months (HR, 0.45).

The analysis also demonstrated statistically significant changes in tumor biology, which were consistent with the mechanism of action of setanaxib. This dataset included 55 patients with recurrent SCCHN and moderate or high CAF-density tumors.

“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 London, consultant clinical oncologist at The Royal Marsden NHS Foundation, London, and investigator on the trial, in the press release.1

In the randomized, placebo-controlled, double-blind trial, the treatment groups were well-balanced and there were no clinically relevant differences seen at baseline between the groups.

Additional findings showed there to be an improvement in disease control rate among those treated with setanaxib at 70% vs 52% in the placebo arm. Further, there was not a significant difference in the primary end point of best percentage change from baseline in tumor size.

Looking at tolerability, setanaxib given in combination with pembrolizumab did not elicit any new safety signals.

"This is a very exciting result which provides clinical evidence of the mode of action of setanaxib in line with our thesis of its antifibrotic 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 Renée Aguiar-Lucander, chief executive officer of Calliditas Therapeutics AB, in the press release.

In the experimental arm of the study, patients were given setanaxib at a dose of 800 mg twice daily along with pembrolizumab at 200 mg given intravenously (IV) every 3 weeks. In the active comparator arm, patients were given placebo throughout the 24-month treatment period along with 200 mg of pembrolizumab given via IV infusion every 3 weeks.2

The trial was open to patients aged ≥18 years with a histologically or cytologically confirmed diagnosis of SCCHN that is recurrent or metastatic with or without nodal involvement and with or without metastatic spread and is not eligible for surgical resection. Patients must have a positive CAFs level, performed at a central laboratory, and have a fresh tumor biopsy taken during or within 30 days prior to the screening period. If available, patients must also have suitable archival tissue which can be used to assess tumor CAFs level and determine patient eligibility. Moreover, patients are required to have measurable disease, a combined positive score ≥1, have their HPV status known at the time of randomization, a life expectancy of at least 6 months in the judgment of the investigator, an ECOG performance status of 0 or 1, and adequate organ and bone marrow function.

Additional trials evaluating setanaxib are ongoing and expected to read out soon. The phase 2 trial of the agent in patients with primary biliary cholangitis is expected to announce results in Q3 of 2024. Additionally, the investigator-led phase 2 trial of setanaxib in patients with idiopathic pulmonary fibrosis is expected to provide topline data in Q4 of 2024. Setanaxib is also being evaluated in an ongoing, phase 2 proof-of-concept trial for the treatment of patients with Alport syndrome. Findings from this study are expected to be released in the first half of 2025.

Moreover, a research and development day is being planned for later this month where the company will provide additional details regarding the phase 2 trial. These data and more support the mechanism of action of setanaxib.

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 6, 2024.
2. A study of setanaxib co-administered with pembrolizumab in patients with recurrent or metastatic squamous cell carcinoma of head and neck (SCCN). Updated April 23, 2024. Accessed May 6, 2024.
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