Cell Therapy Using Genetically Modified Endogenous Immune Cells for Solid Tumors

Solid tumors are cancers that form firm masses in organs or tissues. These include, among others, breast cancer, lung cancer, ovarian cancer, head and neck cancers, and other types of cancer. When such tumors return (recur) after treatment or no longer respond to available standard therapies (refractory), treatment options are often limited, and new therapeutic approaches are needed. IMA203/IMA203CD8 is a TCR-T-cell therapy. In this process, the patient’s own immune cells (T cells) are harvested and genetically engineered in the laboratory so that the immune cells can recognize a tumor marker on cancer cells (PRAME) and specifically target it. PRAME is a tumor-associated antigen that is predominantly found on tumor cells, is scarcely present in healthy tissue, and serves as a target for immunotherapies. For the T cells to recognize the marker, patients must carry the HLA-A*02:01 tissue type: HLA molecules present fragments of proteins from inside the cell on the cell surface, making them visible to T cells. IMA203 can also be combined with nivolumab, an antibody from the class of immune checkpoint inhibitors that blocks the PD-1 receptor on T cells, releases a natural brake on the immune system, and is thus intended to support the immune response against the tumor.

The goal of this Phase 1/2 study is to investigate the safety, tolerability, and efficacy of cell therapy using genetically modified autologous T-cells (IMA203/IMA203CD8) either alone or in combination with nivolumab. As part of the study, patients will be divided into different groups (cohorts) based on their type of disease. In the first part of the study (dose escalation), the drug dose will be gradually increased. This part of the study has already been completed for IMA203. In the second part of the study (dose expansion), patients will receive the recommended drug dose—or the dose confirmed as safe—determined in the first part of the study. In one study group, the IMA203 T-cell therapy will be combined with nivolumab; this group is no longer accepting new patients. Before the cells are reinfused, patients receive preparatory chemotherapy (lymphodepletion with cyclophosphamide and fludarabine), which reduces existing immune cells and creates more space for the reinfused cells. In some groups, the messenger substance interleukin-2 is subsequently administered at a low dose, which can support the survival and proliferation of the T cells. The study is open-label, meaning that study physicians and patients know which medications are being administered. The main objective (primary endpoint) of the study is to assess the safety and tolerability of the treatment; it also investigates whether the tumor responds to the therapy. Follow-up lasts up to five years after cell administration.

Patients aged 18 and older with solid tumors who have already received available standard therapies or who are not suitable for them are eligible to participate. In addition, the HLA-A*02:01 tissue marker and the PRAME tumor marker must be detected. For ovarian, fallopian tube, or peritoneal cancer, as well as uterine cancer, additional tumor-specific diagnostic criteria apply. Patients who are ineligible to participate include, among others, those who have had another cancer diagnosis in the past three years; those with severe autoimmune or heart diseases; those who have previously undergone a stem cell or organ transplant; those with HIV or active hepatitis B/C; those with active brain metastases; and pregnant or breastfeeding women.