In August, the MCW Cancer Center activated a phase 1, multicenter trial, led locally by Mandana Kamgar, MD, MPH, Assistant Professor of Medical Oncology, that evaluates NT-112—a genetically engineered T-cell therapy—in patients with advanced lung, colorectal, pancreatic, and endometrial cancers, or any other solid tumor that is positive for the KRAS G21D mutation. Despite advancements in immunotherapies, such as chimeric antigen receptor (CAR) T-cell therapy, many cancers remain resistant to current treatments. Dr. Kamgar said NT-112 could provide a groundbreaking new immunotherapy option for patients with these hard-to-treat diseases.
“CAR T-cell therapy engineers T-cells to target specific markers on the surface of cancer cells. NT-122 uses a different approach, called T-cell receptor engineering, which can detect both surface and internal cancer cell markers. Unlike pre-made CAR T-cells, NT-122 requires T-cells to be taken from each patient, modified, and reinfused. To be eligible for NT-122, patients must have cancer cells with the KRAS G12D mutation and a specific immune makeup (HLA-C*08:02),” said Dr. Kamgar.
KRAS is a gene that controls cell growth and survival, but certain mutations can cause its constant activation, leading to uncontrolled cell growth and cancer. KRAS mutations are found in up to one-third of cancers, with rates as high as 90-95% in tumors like pancreatic cancer. Targeting KRAS mutations with NT-112 could provide a lifesaving breakthrough for patients without other treatment options.
“Only a small number of patients in this trial will have both the target KRAS G12D mutation and the specific HLA type. We routinely test cancer DNA in all patients with solid tumors and collaborate with companies and cancer societies that also perform HLA typing to help identify the right patients for this study,” added Dr. Kamgar.
The team hopes to enroll up to 10 patients per year at the Froedtert and MCW site.