American Association for Cancer Research
Browse
- No file added yet -

FIGURE 1 from Phase I Trial of Autologous RNA-electroporated cMET-directed CAR T Cells Administered Intravenously in Patients with Melanoma and Breast Carcinoma

Download (198.29 kB)
figure
posted on 2023-05-09, 14:20 authored by Payal D. Shah, Alexander C. Huang, Xiaowei Xu, Robert Orlowski, Ravi K. Amaravadi, Lynn M. Schuchter, Paul Zhang, Julia Tchou, Tina Matlawski, Amanda Cervini, Joanne Shea, Joan Gilmore, Lester Lledo, Karen Dengel, Amy Marshall, E. John Wherry, Gerald P. Linette, Andrea Brennan, Vanessa Gonzalez, Irina Kulikovskaya, Simon F. Lacey, Gabriela Plesa, Carl H. June, Robert H. Vonderheide, Tara C. Mitchell

Study procedures. Participant study procedures including cell collection/manufacturing timeline as well as infusion schedule from eligibility confirmation onward.

Funding

Foundation for the National Institutes of Health (FNIH)

HHS | National Institutes of Health (NIH)

Breast Cancer Research Foundation (BCRF)

History

ARTICLE ABSTRACT

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.

Usage metrics

    Cancer Research Communications

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC