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  • Phase I Trial of Autologous...
    Shah, Payal D; Huang, Alexander C; Xu, Xiaowei; Orlowski, Robert; Amaravadi, Ravi K; Schuchter, Lynn M; Zhang, Paul; Tchou, Julia; Matlawski, Tina; Cervini, Amanda; Shea, Joanne; Gilmore, Joan; Lledo, Lester; Dengel, Karen; Marshall, Amy; Wherry, E John; Linette, Gerald P; Brennan, Andrea; Gonzalez, Vanessa; Kulikovskaya, Irina; Lacey, Simon F; Plesa, Gabriela; June, Carl H; Vonderheide, Robert H; Mitchell, Tara C

    Cancer research communications, 05/2023, Letnik: 3, Številka: 5
    Journal Article

    Treatments are limited for metastatic melanoma and metastatic triple-negative breast cancer (mTNBC). This pilot phase I trial (NCT03060356) examined the safety and feasibility of intravenous RNA-electroporated chimeric antigen receptor (CAR) T cells targeting the cell-surface antigen cMET. Metastatic melanoma or mTNBC subjects had at least 30% tumor expression of cMET, measurable disease and progression on prior therapy. Patients received up to six infusions (1 × 10e8 T cells/dose) of CAR T cells without lymphodepleting chemotherapy. Forty-eight percent of prescreened subjects met the cMET expression threshold. Seven (3 metastatic melanoma, 4 mTNBC) were treated. Mean age was 50 years (35-64); median Eastern Cooperative Oncology Group 0 (0-1); median prior lines of chemotherapy/immunotherapy were 4/0 for TNBC and 1/3 for melanoma subjects. Six patients experienced grade 1 or 2 toxicity. Toxicities in at least 1 patient included anemia, fatigue, and malaise. One subject had grade 1 cytokine release syndrome. No grade 3 or higher toxicity, neurotoxicity, or treatment discontinuation occurred. Best response was stable disease in 4 and disease progression in 3 subjects. mRNA signals corresponding to CAR T cells were detected by RT-PCR in all patients' blood including in 3 subjects on day +1 (no infusion administered on this day). Five subjects underwent postinfusion biopsy with no CAR T-cell signals seen in tumor. Three subjects had paired tumor tissue; IHC showed increases in CD8 and CD3 and decreases in pS6 and Ki67. Intravenous administration of RNA-electroporated cMET-directed CAR T cells is safe and feasible. Data evaluating CAR T therapy in patients with solid tumors are limited. This pilot clinical trial demonstrates that intravenous cMET-directed CAR T-cell therapy is safe and feasible in patients with metastatic melanoma and metastatic breast cancer, supporting the continued evaluation of cellular therapy for patients with these malignancies.