Dr Luke Explains IMA203, a Novel Agent for Metastatic Melanoma

In an interview with Targeted Oncology, Jason Luke, MD, FACP, associate director for clinical research at the Hillman Cancer Center at the University of Pittsburgh, discusses the mechanism of action of IMA203.

IMA203 is an autologous TCR-T (T-cell receptor-engineered T-cell) therapy. This means it uses a patient's own T-cells, which are then genetically modified to express a specific T-cell receptor. IMA203 is designed to target PRAME, an intracellular protein that is displayed as a peptide antigen on the surface of various solid tumors, including melanoma, at high density.

There is a critical need for new therapies for unresected or metastatic melanoma, especially in patients who have relapsed after initial checkpoint inhibitor treatment. These patients often experience frequent recurrence and limited long-term survival, highlighting the need for treatments that can achieve deeper and more durable responses. IMA203 aims to address this unmet need.

Luke explains that patients are identified as HLA A*2:01 genotype. Then, clinicians can then take blood via leukapheresis in order to use a lentiviral transfection to insert a T-cell receptor into the patient's blood against the cancer antigen PRAME.

This is a conceptually different approach in adoptive cell transfer, as compared with tumor infiltrating lymphocyte (TIL) therapy like lifileucel (Amtagvi). There, patients have a tumor harvest by surgery, and immune cells from the tumor are grown in the lab. By contrast, for TCR therapy, blood is removed by leukapheresis and then cells are genetically edited to recognize the cancer. Both are very exciting approaches but conceptually are different in terms of how the product is made and what the underlying molecular mechanism is.

An ongoing phase 1a/b trial (NCT03686124) is evaluating IMA203 in patients who are HLA-A*2:01–positive and have PRAME-positive recurrent and/or refractory solid tumors with no other standard-of-care treatments available.