Abstract CT118: CARPETS: A Phase I study of the safety and immune effects of an escalating dose of autologous GD2 chimeric antigen receptor-expressing peripheral blood T cells in patients with GD2-positive metastatic melanoma and refractory solid tumors
Authors: Brown Michael , Gargett Tessa 
Published: August 2019

Abstract
Background: Chimeric antigen receptor (CAR) T cells are genetically engineered to recognize tumor-associated antigens and have potent cytolytic activity against tumors. Adoptive therapy with CAR-T cells has been highly successful in B-cell malignancies but is yet to demonstrate significant clinical benefit in patients with solid tumors. Currently, we are conducting the CARPETS study (ACTRN12613000198729 at www.anzctr.org.au), which is a phase I clinical trial of third-generation GD2-specific CAR-T cells in metastatic melanoma patients at the Royal Adelaide Hospital. This is a world-first trial using CAR T-cell therapy for melanoma and combines a single intravenous infusion of CAR-T cells with standard kinase inhibitor therapy. In vitro correlative studies support cytolytic targeting of melanoma cells by the GD2-CAR-T cells but the ex vivo analyses of study patients’ post-infusion peripheral blood samples indicate poor CAR-T cell expansion and persistence with evidence of an exhausted T-cell phenotype. Further in vitro developmental work has resulted in optimized CAR-T cell manufacturing conditions that now favour generation of GD2-CAR-T cells with a dominant memory phenotype, which may have greater potential for long-term persistence in vivo.
Methods:This trial is open but not recruiting while we await Human Research Ethics Committee approval of a clinical protocol amendment, which is expected by March 2019. Currently, six patients have been recruited of a planned enrolment of 12 patients. Dose escalation has proceeded through three dose levels using a Bayesian continual reassessment method. No dose limiting toxicities were observed in the previously enrolled cohorts. Under the proposed protocol amendment, the remaining six patients will be recruited with eligibility broadened to include other adult GD2-positive malignancies such as bony and soft tissue sarcomas, small cell lung cancer, and triple negative breast cancer. In future correlative studies, the purpose of the additional patient recruitment will be to compare the in vivo expansion and persistence of GD2-CAR-T cells, which will now be manufactured to carry the favorable memory phenotype, with previously transferred GD2-CAR-T cells, the manufacture of which was associated with the unfavorable exhausted phenotype. Because of the potential risk of additional toxicity conferred by the altered ex vivo CAR-T cell manufacturing conditions, dose escalation will proceed from dose level 2 and lympho-depleting chemotherapy will not be given. The next data analysis will be related to completed dose escalation using CAR-T cell products manufactured according to the new conditions.
Citation Format: Michael Brown, Tessa Gargett. CARPETS: A Phase I study of the safety and immune effects of an escalating dose of autologous GD2 chimeric antigen receptor-expressing peripheral blood T cells in patients with GD2-positive metastatic melanoma and refractory solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT118.