Autologous Glypican 3-Targeted, Armored CAR T Cells in Patients with Advanced Solid Tumors: A Phase I Dose-Escalation Study of TAK-102
Authors:
- Yasutoshi KubokiYasutoshi Kuboki
- Takafumi KoyamaTakafumi Koyama
- Masafumi IkedaMasafumi Ikeda
- Tomoyuki SatakeTomoyuki Satake
- Takeshi SawadaTSTakeshi Sawada
- Yutaka ShimazuYutaka Shimazu
- Shunsuke KondoShunsuke Kondo
- Yuki KatsuyaYuki Katsuya
- Hideaki KageharaHKHideaki Kagehara
- Takenori AkaikeTATakenori Akaike
- Aman SinghAman Singh
- Kondala AtkuriKAKondala Atkuri
Open Access
- 26 October 2026
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Immunology Research
- p. OF1-OF12
Abstract
Chimeric antigen receptor (CAR) T-cell therapies have shown limited promise in solid tumors owing to the immunosuppressive tumor microenvironment. TAK-102 is a next-generation, glypican 3 (GPC3)-targeted CAR T-cell therapy engineered to coexpress IL7 and chemokine ligand 19 (CCL19), enhancing T-cell survival and trafficking. In this first-in-human, open-label, phase I, dose-escalation study (ClinicalTrials.gov: NCT04405778), we evaluated a single TAK-102 infusion in 11 patients with GPC3+ advanced solid tumors refractory or intolerant to standard therapies. Patients received TAK-102 at one of three dose levels following leukapheresis and lymphodepletion chemotherapy. The primary endpoints were the incidences of dose-limiting toxicities, treatment-emergent adverse events (TEAE), and adverse events of special interest. No dose-limiting toxicities were observed. The most common TEAEs were hematologic, including neutropenia and leukopenia (81.8%), and cytokine release syndrome (54.5%), all grade 1 to 2. No objective responses were observed; however, five patients achieved stable disease (disease control rate, 45.5%). One patient had a 26.1% reduction in tumor size lasting 9 months, accompanied by a 51.6% decline in serum α-fetoprotein. Cellular kinetics showed dose-dependent expansion, with the highest exposure at 5 × 108 CAR+ cells/body. Posttreatment biopsies revealed increased CD8+ T-cell infiltration and activation markers, although CAR+ cells were undetectable in tumor tissue. Serum CCL19 levels increased with dose, suggesting immune priming. These findings support a manageable safety profile for TAK-102 and provide early evidence of biological activity in solid tumors. Further studies are warranted to optimize dosing, improve CAR T-cell persistence, and evaluate efficacy in larger patient cohorts.Keywords
Funding Information
- Takeda Pharmaceutical Company Limited