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Clinical Studies

Impact of concomitant medications on efficacy of CLDN18.2-specific CAR-T cell therapy in advanced gastric cancer

British Journal of Cancer volume 134, pages 439–446 (2026)Cite this article

Subjects

Abstract

Background

Claudin18.2 (CLDN18.2)-specific CAR-T cell therapy has demonstrated promise in advanced gastric cancer (GC). However, the impact of concomitant medications on the efficacy outcomes remains unclear.

Methods

We retrospectively analyzed advanced GC patients receiving CLDN18.2-specific CAR-T cell therapy from a phase I trial. Concomitant medications were defined as any drugs administered within 30 days before and after CAR-T cell infusion, including corticosteroids, antibiotics, tocilizumab, granulocyte colony-stimulating factor (G-CSF), thrombopoietin (TPO), and erythropoietin. Metagenomic sequencing was employed to elucidate the differences in gut microbiome signatures between responders and non-responders.

Results

Of 72 patients included in the study, 6 (8.3%) received corticosteroids, 49 (68.1%) received tocilizumab, and 22 (30.6%) received antibiotics, 15 (20.8%) received G-CSF, 5 (6.9%) received thrombopoietin, and no patient received erythropoietin. The median progression-free survival (PFS) (2.6 vs. 5.8 months; P < 0.001) and overall survival (OS) (3.9 vs. 9.5 months; P < 0.001) were significantly shorter for patients who received antibiotics for infection compared to those who did not. No significant differences were observed in objective response rate (ORR), PFS, and OS between patients who received corticosteroids, tocilizumab, antibiotics for prophylaxis, G-CSF, or TPO and those who did not. A higher abundance of Fusobacterium nucleatum, Lactobacillus mucosae, Prevotella pallens, and Streptococcus pseudopneumoniae in gut microbiome was associated with a superior treatment response.

Conclusions

The study indicates that the use of antibiotics for infection reduces the efficacy outcomes of CLDN18.2-specific CAR-T cell therapy for advanced GC, while other concomitant medications do not affect the outcomes. Further research is needed to clarify the optimal administration of these medications and the underlying mechanisms of the gut microbiome in impacting CAR-T treatment response.

Trial registration

NCT03874897

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Fig. 1: Kaplan–Meier curves of progression-free survival (PFS) in advanced gastric cancer patients treated with CLDN18.2-specific CAR-T cells according to exposure to different concomitant medications.
Fig. 2: Kaplan–Meier curves of overall survival (OS) in advanced gastric cancer patients treated with CLDN18.2-specific CAR-T cells according to exposure to different concomitant medications.
Fig. 3: Gut microbiome composition associated with CLDN18.2-specific CAR-T treatment response.

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Data availability

Requests for individual participant-level data from this study should be submitted via email to the corresponding author with detailed proposals.

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Acknowledgements

We thank all the participants and their families in this trial.

Funding

This study was funded by National Natural Science Foundation of China (No. 92459302, No. 82522068, and No. U22A20327), National Key Research and Development Program of China (No. 2025YFC3409800, No. 2023YFC3403700, and No. 2022YFA0912400), Beijing Natural Science Foundation (L232080), Beijing Hospitals Authority Youth Program (QMS20201101), Science Foundation of Peking University Cancer Hospital (JC202406), Clinical Medicine Plus X - Young Scholars Project of Peking University, Peking University Clinical Scientist Training Program, Fundamental Research Funds for the Central Universities, and CARsgen Therapeutics Co., Ltd.

Author information

Author notes

  1. These authors contributed equally: Jiarui Li, Lian Liu, Min Tao, Zihan Han.

Authors and Affiliations

  1. Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumors, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China

    Jiarui Li, Lian Liu, Min Tao, Zihan Han, Mingyang Ma & Lei Jiang

  2. Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumors, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing, China

    Chang Liu, Dan Liu, Panpan Zhang, Miao Zhang & Ran Xue

  3. Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumors, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing, China

    Jifang Gong, Xiaotian Zhang & Lin Shen

  4. Beijing Key Laboratory of Cell & Gene Therapy for Solid Tumors, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Centre, Peking University Cancer Hospital & Institute, Beijing, China

    Changsong Qi

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Contributions

JL, LL, MT, ZH, and MM collected the data. JL drafted the manuscript. JL and ZH performed the statistical analyses. CQ, XZ, and LS conceived and designed the trial. CQ, XZ, and LS reviewed and revised the manuscript. All authors read and approved the final version of the manuscript.

Corresponding authors

Correspondence to Xiaotian Zhang, Lin Shen or Changsong Qi.

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The authors declare no competing interests.

Ethics approval and consent to participate

The study was approved by the Ethics Committee of Peking University Cancer Hospital (2018YJZ75). The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. All patients provided written informed consent before participation in this trial

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Li, J., Liu, L., Tao, M. et al. Impact of concomitant medications on efficacy of CLDN18.2-specific CAR-T cell therapy in advanced gastric cancer. Br J Cancer 134, 439–446 (2026). https://doi.org/10.1038/s41416-025-03289-7

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