Updated results from first-in-human phase 1 dose-escalation trial of TAK-102, a GPC3-targeted armored CAR T cells, in patients with advanced solid tumors.

作者：Takako Eguchi Nakajima, Yasutoshi Kuboki, Masaru Fukahori, Yutaka Shimazu, Shunsuke Kondo, Yuki Katsuya, Masafumi Ikeda, Tomoyuki Satake, Hideaki Kagehara, Takenori Akaike, Aman P. Singh, Kondala R. Atkuri, Petar Pop-Damkov, Koji Tamada, Takafumi Koyama · 发表于：Journal of Clinical Oncology · 年份：2024 · DOI：10.1200/jco.2024.42.16_suppl.2543 · 被引用次数：16 · 研究领域：CAR-T cell therapy research、Biosimilars and Bioanalytical Methods、Immunotherapy and Immune Responses

2543 Background: Glypican 3 (GPC3) is a member of the glypican family of heparan sulfate proteoglycans that are attached to the cell surface by a glycosylphosphatidylinositol anchor. High GPC3 expression rates are reported in numerous cancer types with a high unmet medical need, including hepatocellular carcinoma (HCC). TAK-102 is a GPC3-targeted autologous chimeric antigen receptor T cell (CAR-T) immunotherapy armored with IL-7 and CCL19. The addition of IL-7 and CCL19 to the construct was designed to support the expansion of memory subsets and persistence of CAR-T cells. We hypothesized TAK-102 would help overcome the challenges associated with an immunosuppressive tumor microenvironment that limit the activity of nonarmored CAR-T therapies in solid tumors. Methods: The first-in-human, Phase 1 dose escalation study evaluated TAK-102 in patients (pts) with GPC3-expressing solid tumors who were refractory or intolerant to standard treatments. TAK-102 was administered via a single infusion to 3 dose cohorts after lymphodepleting chemotherapy (LDC; consisting of fludarabine and cyclophosphamide): dose level (DL) 1 (starting cohort), 1x10 7 CAR+ cells/body; DL2, 1x10 8 CAR+ cells/body; DL3, 5x10 8 CAR+ cells/body. Objectives included evaluation of safety, dose-limiting toxicity (DLT), recommended phase 2 dose, cellular kinetic (CK) parameters, tumor markers, cytokine/chemokine and antitumor activity based on RECIST 1.1. Results: Eleven pts were enrolled and infused TAK-102 (DL1:...