Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2025 Jun 17;6(6):102190.
doi: 10.1016/j.xcrm.2025.102190.

Safety and efficacy of perioperative dual PD-1 and HER2 blockade in HER2-positive gastric cancer

Run-Cong Nie  1 , Xiao-Jiang Chen  1 , Cheng-Cai Liang  1 , Bai-Wei Zhao  1 , Wei Wang  1 , Fei-Yang Zhang  1 , Mu-Yan Cai  2 , Hai-Bo Qiu  1 , Zhi-Cheng Xue  1 , Guo-Ming Chen  1 , Zhi-Min Liu  1 , Jun Chi  3 , Jin-Ling Duan  2 , Dong-Sheng Zhang  4 , Ying-Bo Chen  1 , Zhi-Wei Zhou  1 , Yong-Ming Chen  5 , Shu-Qiang Yuan  6 , Yuan-Fang Li  7
Affiliations
Clinical Trial

Safety and efficacy of perioperative dual PD-1 and HER2 blockade in HER2-positive gastric cancer

Run-Cong Nie et al. Cell Rep Med. .

Abstract

The use of trastuzumab and programmed death-1 (PD-1) inhibitor is effective in patients with HER2-positive advanced gastric or gastro-esophageal junction cancer; however, their use has not been investigated in patients with localized disease. This phase 2 trial evaluates the safety and efficacy of dual PD-1 (sintilimab) and HER2 blockade with chemotherapy in patients with resectable HER2-positive gastric and gastro-esophageal junction adenocarcinoma. 22 patients are enrolled, and 20 patients undergo surgery. The primary endpoint is achieved; 12 (55%, 95% confidence interval [CI]: 32-76) of 22 patients have a major pathological response, and 11 (50%, 95% CI: 28-72) of 22 patients achieve pathological complete response. The most common grade 3 treatment-related adverse events are neutropenia and thrombocytopenia. No treatment-related deaths occur. Transcriptomic analysis, bioinformatics analysis, and immunofluorescence staining demonstrate that regulatory T cells are associated with possibility of drug resistance. This study was registered at the Chinese Clinical Trial Registry (identifier: ChiCTR2200058732).

Keywords: HER2; PD-1 inhibitor; gastric cancer; perioperative; trastuzumab.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

None
Graphical abstract
Figure 1
Figure 1
Trial profile
Figure 2
Figure 2
Tumor response and follow-up (A) Waterfall plot of tumor regression to sintilimab, trastuzumab, and chemotherapy. Patients who refused to surgery are not shown (n = 2). (B) Swimmer plot showing the treatment events and follow-up in the intent-to-treat population. GEJ, gastro-esophageal junction; PD-L1, programmed cell death-ligand 1; CPS, combined positive score; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; FISH, fluorescence in situ hybridization; EBV, Epstein-Barr virus.
Figure 3
Figure 3
Immune cell landscape of patients at baseline and after neoadjuvant treatment (A and B) Heatmaps depicting 22 immune cell types at baseline and after neoadjuvant treatment in patients who achieved an MPR (A) and those who did not (B). (C–F) Analysis of CD8 T cell (C), follicular helper T cell (Tfh) (D), regulatory T cell (Tregs) (E), and γδT cell (F) infiltration at baseline and after neoadjuvant treatment in patients who achieved an MPR (left, N = 12) and those who did not (right, N = 9). (G) Immunofluorescence staining and quantification of Tregs at baseline and after neoadjuvant treatment in patients who achieved an MPR (N = 12) and those who did not (N = 6). MPR, major pathological response. Wilcoxon rank-sum test.
See this image and copyright information in PMC

References

    1. Bray F., Laversanne M., Sung H. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2024;74:229–263. - PubMed
    1. Sano T., Coit D.G., Kim H.H., Roviello F., Kassab P., Wittekind C., Yamamoto Y., Ohashi Y. Proposal of a new stage grouping of gastric cancer for TNM classification: International Gastric Cancer Association staging project. Gastric Cancer. 2017;20:217–225. - PMC - PubMed
    1. Ajani J.A., D'Amico T.A., Bentrem D.J., Chao J., Cooke D., Corvera C., Das P., Enzinger P.C., Enzler T., Fanta P., et al. Gastric Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology. J. Natl. Compr. Canc. Netw. 2022;20:167–192. - PubMed
    1. Lordick F., Carneiro F., Cascinu S., Fleitas T., Haustermans K., Piessen G., Vogel A., Smyth E.C., ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org Gastric cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann. Oncol. 2022;33:1005–1020. - PubMed
    1. Al-Batran S.E., Homann N., Pauligk C., Goetze T.O., Meiler J., Kasper S., Kopp H.G., Mayer F., Haag G.M., Luley K., et al. Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial. Lancet. 2019;393:1948–1957. - PubMed

Publication types

MeSH terms