In the context of the IACT program, two types of clinical studies will be performed. Both involve the use of an agonist IS-Ab that is directed against the immune-stimulatory receptor CD40. This antibody has already been tested in patients and was found to be well-tolerated. Now that this is known, the plan is to test, by means of clinical trials, whether this antibody can stimulate anti-cancer immunity in humans. The design of these trials are based on experimental observations in mice and reflect situations in which anti-CD40 antibodies were found to have a strong stimulatory effect on anti-tumor immunity that was accompanied by tumor regression.
The first study will be performed in patients with pancreatic ductal adenocarcinoma, the most common type of pancreatic cancer. These patients will receive the anti-CD40 antibody in combination with the mild chemotherapeutic drug gemcitabine. Pre-clinical tests in tumor-bearing mice have shown that these drugs act synergistically on the anti-tumor immune response and against the tumor.
The second study will be performed in patients with head and neck cancer, in particular patients of which the tumor is known to be positive for a cancer-inducing virus, human papillomavirus type 16 (HPV16). The fact that the tumor is positive for HPV16 offers the opportunity to treat these patients with a highly potent vaccine that induces immune responses against these viral antigens and that, because the tumor is positive for this virus, can attack the tumor. Nevertheless, we have learned from prior pre-clinical and clinical studies that vaccination alone is unlikely to be sufficient for inducing an immune response that is strong enough to cause tumor regression. However, we do know from mouse experiments that combination of such vaccines with agonist anti-CD40 IS-Abs can result in 10-100-fold increases in the vaccine-induced response and can lead to further changes in the immune system that make tumors more permissive to immune attack. Consequently, we plan to treat patients with HPV16-positive head and neck cancer with a combination of the HPV16 vaccine and anti-CD40 agonist IS-Ab.
More information on the aforementioned studies will be provided 2-3 months prior to the opening of these trials. The trial in pancreatic cancer will run at the University Hospitals in Heidelberg, Germany and Southampton, United Kingdom. The trial with head and neck cancer will run at the University Hospitals in Southampton, United Kingdom and Pamplona, Spain. All three clinics are highly experienced in conducting cancer treatment and performing clinical trials.
Please consult your physician for more information on these trials and potential eligibility for participation.