Immunocore Holdings has initiated Phase 1 trials for two novel immunotherapies, IMC-P115C and IMC-R117C, targeting PRAME and PIWIL1 respectively, in patients with advanced cancers. These trials mark a significant step in Immunocore's development of ImmTAC (Immune mobilising monoclonal TCRs Against Cancer) molecules, a class of bispecific biologics engineered to target intracellular cancer antigens and activate T-cells to kill malignant cells.
IMC-P115C: A Half-Life Extended ImmTAC Targeting PRAME
Immunocore's IMC-P115C, a half-life extended ImmTAC candidate, has entered a Phase 1 dose escalation trial. This trial aims to evaluate the safety, pharmacokinetics, and clinical activity of IMC-P115C in HLA-A02:01-positive patients with a range of advanced cancers expressing PRAME (PReferentially expressed Antigen in MElanoma). IMC-P115C is designed to improve patient convenience by reducing the frequency of treatment administration, representing Immunocore’s first half-life extended candidate to enter the clinic. The molecule targets the same HLA-A02:01 PRAME peptide as brenetafusp.
IMC-R117C: Targeting PIWIL1 in Gastrointestinal Cancers
In a separate development, Immunocore has dosed the first subject in a multicenter Phase I/II trial of IMC-R117C, a PIWIL1-targeted immunotherapy, for treating colorectal and other gastrointestinal cancers. This open-label, first-in-human trial will evaluate the therapy’s clinical activity and safety in HLA-A*02:01-positive subjects with select advanced solid tumors. The trial is also designed to assess various aspects of the therapy, including tolerability, pharmacokinetics (PK), immunogenicity, and pharmacodynamics. IMC-R117C will be assessed as both a single agent and in conjunction with other therapies.
According to Immunocore, PIWIL1 is overexpressed in various malignancies and associated with aggressive tumor growth. Mohammed Dar, Clinical Development senior vice-president, and chief medical officer at Immunocore, stated that PIWIL1 is expressed across all major subsets of colorectal cancer, including microsatellite-stable CRC, which has historically been insensitive to immunotherapy.
ImmTAC Technology: A Novel Approach to Cancer Immunotherapy
Immunocore's ImmTAC molecules represent a novel approach to cancer immunotherapy. These soluble TCRs are specifically engineered to identify intracellular cancer antigens and kill malignant cells through an anti-CD3 immune-activating effector function. This mechanism of action, which includes T-cell infiltration into human tumors, offers the potential to treat hematologic and solid tumors, including those with low mutation rates or immune 'cold' tumors.
With nine active clinical and pre-clinical programs covering infectious and autoimmune diseases, as well as oncology, Immunocore continues to advance its ImmTAC platform. KIMMTRAK, the company’s lead TCR therapeutic, has already gained approval in several regions for the treatment of a specific type of melanoma, underscoring the potential of this innovative technology.
