Phase I/IIa Study of Immunization With Frameshift Peptides Administered With Montanide® ISA-51 VG in Patients With Advanced MSI-H Colorectal Cancer
The present study is initiated to evaluate vaccination with MSI-specific FSPs in patients
with MSI-H colorectal cancer. Specifically, the present study aims at the following
- Evaluation of potential toxicity of the FSP AIM2(-1), HT001(-1), TAF1B(-1)
- Evaluation of the immune response in patients with advanced MSI-H colorectal cancer
before vaccination and after vaccination with the FSP AIM2(-1), HT001(-1), TAF1B(-1)
In this context, the present study shall demonstrate whether application of FSP in a
vaccination approach is associated with the induction of peptide-related toxicity. Hence,
the study marks the first step towards the application of FSP in humans, as it provides
information on the safety of FSP as vaccination agents for the first time. Moreover, the
study shall provide initial information, whether vaccination with FSP can induce
FSP-specific immune responses in patients with MSI-H colorectal cancer. Thus, it shall
provide information, whether FSPs AIM2(-1), HT001(-1), and TAF1B(-1) have the potential to
elicit peptide-specific immune responses and therefore represent suitable targets for the
induction of tumor antigen-specific immune responses in patients with MSI-H tumors.
The present study marks an important milestone towards a potential application of
MSI-specific FSP as therapeutic agents in the management of patients with MSI-H tumors,
particularly patients with MSI-H colorectal cancer. Long-term goal of this approach is to
develop novel tools for (1) the palliative and/or adjuvant therapy of patients with advanced
MSI-H colorectal cancer and (2) the preventive application of FSPs in mutation carriers of
the HNPCC/Lynch syndrome.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Safety as assessed by number and severity of adverse events categorized according to CTC criteria v4.0 and the probability of the induction of immune tolerance. Immune tolerance is defined as significant and sustained decline of antigen-specific cellular immune responses after vaccination compared to the antigen-specific cellular immune response measured before vaccination , as assessed by Interferon-gamma (IFN-g) ELISpot using assay-specific cut-off values.
up to 8 months
Elke Jäger, Prof. Dr.
Krankenhaus Nordwest Frankfurt