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Chimeric Antigen Receptor (CAR) T-cell Therapy with iC9-CAR.B7-H3 T-cells for the Treatment of Refractory Pancreatic Ductal Adenocarcinoma

Trial Status: active

This phase I trial studies the safety, side effects, and best dose of autologous T lymphocyte chimeric antigen receptor (CAR) cells targeted against the B7-H3 antigen and containing inducible caspase 9 safety switch (iC9-CAR.B7-H3 T-cells) for the treatment of pancreatic ductal adenocarcinoma (PDAC) that does not respond to treatment (refractory). PDAC tumor cells carry a substance on their surface called B7-H3. Normal (healthy) cells very rarely carry the B7-H3 substance on their surface. CAR T-cell therapy is a type of treatment in which a patient's own T-cells are taken from their blood and genetically modified to create a special receptor so they can recognize and attack pancreatic tumor cells. This special receptor is called the anti-B7-H3 antibody. This antibody attaches to tumor cells that carry the B7-H3 substance on their surface. Once the anti-B7-H3 antibody attaches to the cancerous cells, it is hoped that the modified T-cells will attack and destroy them. Because modified CAR T-cells are different from normal T-cells, it is possible that a person's own immune system may attack and destroy them, so they may not stay very long in the body. To prevent this from happening, lymphodepletion therapy with cyclophosphamide and fludarabine is used before receiving iC9-CAR.B7-H3 T-cells. Chemotherapy drugs, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Lymphodepletion is a type of chemotherapy that been shown to increase the amount of time that the modified CAR T-cells survive in the body and have been associated with improved cancer-free survival. The iC9-CAR.B7-H3 T-cells also have an extra component called the iC9 switch. The body may react when the modified CAR-T-cells are given, and patients may experience unpleasant side effects such as fever and pain. Sometimes these side effects do not go away with normal treatments. If these side effects do occur and there is no other way to adequately treat them, it is possible to shut down the modified CAR-T-cells and stop their activity inside the patient's body. If that is needed, the iC9 switch is activated by giving an investigational drug called rimiducid. Once the modified CAR-T-cells are turned off, they will no longer have any effect in fighting cancerous cells in the body. Giving iC9-CAR.B7-H3 T-cells following lymphodepleting chemotherapy with cyclophosphamide and fludarabine may be safe, tolerable, and/or effective for the treatment of refractory PDAC.