Clinical studies

The IACT project encompasses two clinical studies closely reflecting pre-clinical treatment settings in which agonist anti-CD40 IS-Abs were shown to be highly effective in enhancing the anti-tumor immune response and in inducing tumor regression.

IAPACA trial (Immunostimulatory Antibodies for Treatment of Pancreatic Cancer):

Cancer type: Pancreatic ductal adenocarcinoma (PDA)
Treatment concept: administration of agonist anti-CD40 IS-Ab ChiLob7/4, targeting the CD40 receptor on several immune cell subsets, in combination with standard 28-week cycles of gemcitabine

HARE-40 trial (HPV Anti-CD40 RNA vaccine):

Cancer Type: human papillomavirus type 16 (HPV16) positive head and neck squamous cell carcinoma (HNSCC)
Treatment concept: administration of agonist anti-CD40 IS-Ab ChiLob7/4, targeting the CD40 receptor on several immune cell subsets, in combination with an mRNA-based vaccine against HPV16-derived tumor antigens.

The main aim of these studies will be to carefully evaluate whether the pre-clinical results translate into similar outcome in human cancer patients. The first step in this respect is to analyze whether the immunotherapeutic treatments concerned can enhance the anti-tumor immune response in humans, as this would be the best indication that the treatments also have the potential to induce tumor regression. Notably, based on current clinical experience with the aforementioned checkpoint inhibitors, it is likely that an extended treatment schedule is required to cause durable clinical responses. However, studies with primary curative intent involving prolonged treatment and larger patient numbers should preferably not be started before evidence is obtained that the treatments have their primary intended impact: enhancement of anti-tumor immunity.

In view of these considerations, the trials scheduled are so-called pharmacodynamic (PD) biomarker studies in which the biological impact of a short treatment protocol will be analyzed in great detail on basis of parameters related to the strength and quality of the immune response as well as to the growth and vitality of the tumor. While these biomarker tests constitute the primary endpoint of the trials, clinical responses will be a prominent secondary endpoint.