RE001 T Cell Injection for the Treatment of KRAS G12V Mutated Solid Tumors

At present, there is an urgent need for new drugs for kirsten rat sarcoma viral oncogene (KRAS) mutant tumors in clinic. Preclinical studies support the specificity, safety and anti-tumor activity of RE001. Previous similar studies suggest the feasibility of T cell receptor engineered T cell therapy (TCR-T) treatment, and measures have been taken to ensure the safe administration of RE001 and the close monitoring and management of adverse events. To sum up, RE001 has controllable safety and anti-tumor activity on KRAS mutant solid tumor, which can be preliminarily studied to provide support for clinical research of patients with advanced solid tumor.

This study is a single-center, open, single-arm, dose-increasing, single-dose phase I clinical trial of safety and tolerance. It is planned to recruit 30 patients with advanced malignant solid tumor with KRAS G12V mutation. In this experiment, 3+3 dose increasing design was adopted, and the dose increasing scheme was as follows (deviation 30%): low dose group: 4×109, middle dose group: 8×109, and high dose group: 1.6×1010. At least 21 days before T cell infusion, peripheral blood mononuclear cell (PBMC) (about 1×10\^9) of the subjects were collected by a single blood cell separator. After gene editing, these cells were amplified in vitro and infused into the subjects after reaching the target number. The evaluation period of dose-limited toxicity (DLT) was 28 days after the first administration of each dose group. The subjects were administered at intervals, and the interval of administration began from the day of TCR-T cell infusion of the previous subject to the day of TCR-T cell infusion of the next subject. The interval between the first three subjects in the same dose group and the next subject (the same group or different groups) is at least 14 days; If one third of the subjects in the dose group have DLT, and three new subjects need to be added, the interval with the next subject (same group or different group) should be at least 21 days. All the subjects who met the entry and exit criteria and signed the informed consent form were observed in hospital at the beginning of lymphocyte clearance chemotherapy, with the dosage of cyclophosphamide (600-800mg/m\^2/days,-5,-4 days) and fludarabine (25-30mg/m\^2/days,-5,-4,-3 days), at least two days after the completion of lymphocyte clearance chemotherapy. During the trial, the subjects can withdraw from the study at any time for any reason, which will not affect the subsequent treatment and care of the subjects by medical staff or medical institutions.