Carbon nanoparticle-Fe (II) complex for ferroptosis therapy in refractory solid tumors: a phase I trial.

Huashan Shi, Ping Xie, Xiaoyu Li, Lin Lai, Qi Dang, Zehui Gou, Zhengyin Liao, Qing He, Wenhao Guo, Zhenyu Ding, Songpu Wu, Yueyun Chen, Zhen Lin, Ying Wen, Yuanfang Huang, Yan Chen, Jianqiang Xu, Chuying Huang, Yongsheng Wang

Journal: Signal transduction and targeted therapy 2026;11(1):

PMID: 42816483

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Abstract

We developed a novel carbon nanoparticle-Fe (II) complex prepared via suspension injection (CNSI-Fe) to induce cancer cell ferroptosis through direct intratumoral delivery of ferrous iron. Preclinical studies have demonstrated that CNSI-Fe has promising antitumour effects, thereby prompting this first-in-human, single-arm, open-label, dose-escalation phase I trial in patients with refractory solid tumors. Primary objectives included assessments of safety and tolerability and the determination of dose-limiting toxicity (DLT) and the maximum tolerated dose (MTD). Secondary objectives included the determination of preliminary antitumour efficacy and pharmacokinetics. Applying a 3 + 3 design across five doses (30-150 mg), a total of 19 enrolled patients received CNSI-Fe treatment. The MTD was not reached, and only one patient (in the 90 mg cohort) experienced DLT events. For all treated patients (n = 19), the common adverse events included injection site pain (89.5%), hypertension (52.6%), elevated serum iron levels (47.4%), and anemia (47.4%). Pharmacokinetic analysis revealed rapid iron absorption (peak time: 0.15-0.41 h) and clearance (half-life: 1.96-5.06 h), with peak serum concentrations ranging from 3520.33 to 13961.67 ng/mL. Preliminary efficacy estimates revealed an overall response rate of 10.5% and a disease control rate (DCR) of 84.2%. Notably, the DCR reached 100% in patients with lymph node and sarcoma lesions. Overall, CNSI-Fe demonstrated a favorable safety profile and promising antitumour activity (ClinicalTrials.gov identifier: NCT06048367), supporting further investigations in a phase II trial.

Address: Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.; Sichuan Enray Pharmaceutical Sciences Company, Chengdu, China.; Clinical Trial Center, National Medical Products Administration Key Laboratory for Clinical Research and Evaluation of Innovative Drugs, West China Hospital, Sichuan University, Chengdu, China.; Department of Oncology, Hubei Key Laboratory for Translational Research in Traditional Chinese Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China.; Phase I Clinical Research Center, Shandong First Medical University Affiliated Tumor Hospital, Jinan, China.; Department of Medical Ultrasound, West China Hospital, Sichuan University, Chengdu, China.; Department of Abdominal Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.; Department of Head and Neck Oncology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, China.; Department of Emergency Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.; School of Chemical Engineering, Ocean Technology and Life Science (CEOTLS) & Panjin Institute of Industrial Technology (PIIT), Dalian University of Technology, Panjin, China.; Department of Oncology, Hubei Key Laboratory for Translational Research in Traditional Chinese Medicine, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China. [email protected].; Institute of Herbgenomics, Chengdu University of Traditional Chinese Medicine, Chengdu, China. [email protected].; Department of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. [email protected].; Division of Thoracic Tumor Multimodality Treatment, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. [email protected].

DOI: 10.1038/s41392-026-02929-5

MeSH Terms: Humans, Female, Male, Neoplasms, Nanoparticles, Middle Aged, Ferroptosis, Adult, Aged, Maximum Tolerated Dose, Carbon, Iron, Ferrous Compounds