Combination treatment with anti-HER2 therapeutic antibody RC48, PD-1 inhibitor, radiotherapy, and granulocyte macrophage-colony stimulating factor (GMCSF) in patient with metastatic gastric cancer - a case report

Sep 21, 2026

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Combination treatment is evaluated in a case report involving a patient with HER2-positive, PD-L1-negative metastatic gastric cancer. The study uses a four-part regimen that integrates a novel anti-HER2 antibody (RC48) with a PD-1 inhibitor, radiotherapy, and granulocyte macrophage-colony stimulating factor (GM-CSF), following a PRaG approach. After rapid progression on prior surgery and multiple trastuzumab plus chemotherapy courses, the patient showed a positive response after two treatment cycles and achieved a progression-free survival of 6.5 months, supporting the potential of four-combination strategies and the importance of carefully selected radiation dosing for dual-target immunotherapy.

LanguageEnglish

CategoryHealthcare

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Pages10

Reading Time25 min

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Introduction

HER2-positive metastatic gastric cancer background and limitations of standard therapy

Immunotherapy with PD-1/PD-L1 inhibitors in metastatic gastric cancer

Role of radiotherapy and stereotactic body radiotherapy (SBRT) in immune activation

Study rationale for combining RC48, PRaG regimen, and radiation strategies

TYPE Case Report PUBLISHED 01 February 2024 DOI 10.3389/fimmu.2024.1321946 OPEN ACCESS EDITED BY Yih-Horng Shiao, United States Patent and Trademark Ofﬁce, United States REVIEWED BY Liyuan Zhang, Second Afﬁliated Hospital of Soochow University, China Amin Nassar, Yale New Haven Health System, United States *CORRESPONDENCE Yang Yang [doctoryang1985@163.com](doctoryang1985@163.com) †These authors have contributed equally to this work and share ﬁrst authorship RECEIVED 15 October 2023 ACCEPTED 19 January 2024 PUBLISHED 01 February 2024 CITATION Liu Z, Wang F, Zhang Y, Lu J and Yang Y (2024) Combination treatment with antiHER2 therapeutic antibody RC48, PD-1 inhibitor, radiotherapy, and granulocyte macrophage-colony stimulating factor (GMCSF) in patient with metastatic gastric cancer: a case report. Front. Immunol. 15:1321946 . doi: 10.3389/fimmu.2024.1321946 COPYRIGHT © 2024 Liu, Wang, Zhang, Lu and Yang. This isan open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Combination treatment with anti-HER2 therapeutic antibody RC48, PD-1 inhibitor, radiotherapy, and granulocyte macrophage-colony stimulating factor (GM-CSF) in patient with metastatic gastric cancer: a case report Zhuixing Liu 1†, Fang Wang2†, Yingqi Zhang 2, Jun Lu 2 and Yang Yang 2* 1 Department of Oncology, Xi‘an International Medical Center Hospital, Xi ‘an, China, 2 Department of Radiotherapy & Oncology, Xi‘an International Medical Center Hospital, Xi‘an, China HER2 overexpression/ampliﬁcation is a prevalent driver in various types of cancer, including gastric cancer (GC) . Limited options are available for patients with HER2-positive metastatic gastric cancer, particularly those who do not respond to the standard therapy of HER2 antibody trastuzumab combined with chemotherapy. Previous research suggests that combining a PD-1 inhibitor with radiotherapy and granulocyte macrophage-colony stimulating factor (PRaG regimen) may enhance the antitumor effects in patients with chemotherapyresistant metastatic solid tumors. In this case study, we presented a potential treatment strategy of a patient having HER2-positive and PD-L1-negative gastric adenocarcinoma. The patient showed rapid tumor progression even after surgery and multiple trastuzumab plus chemotherapy treatments. To address this, we employed a novel anti-HER2 antibody called RC48 in combination with PRaG regimen therapy (PRaG3 . 0) . The patient demonstrated a positive response after two treatment cycles and achieved a progression-free survival time of 6.5 months. This case highlights the potential of four-combination therapies for treating refractory, multiorgan, HER2-positive, PD-L1-negative metastatic gastric cancer. Additionally, varying radiation doses in targeting dual foci is critical to enhance tumor immunotherapy. KEYWORDS RC48, PD-1 inhibitor, stereotactic body radiotherapy, GM-CSF, gastric cancer, HER2-positive Frontiers in Immunology 01 [frontiersin.org](frontiersin.org) 1 Introduction According to the ﬁndings from Global Cancer Statistics 2020, gastric cancer (GC) is the ﬁfth most commonly diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide (1) . In China, there are over 20,000 new cases of GC each year, with approximately 170,000 deaths attributed to this disease, accounting for about 25% of all cancer-related deaths (2) . Around 20% of GC patients show an overexpression of human epidermal growth factor receptor 2(HER2) (3) . The phase III ToGA trial has conﬁrmedtrastuzumab as the approved medication to be included in the

FAQs

What treatment combination is used in this case report?

The case report describes a four-combination strategy using anti-HER2 antibody RC48 together with a PD-1 inhibitor, radiotherapy, and GM-CSF within a PRaG regimen framework.

Why was this regimen chosen for the patient?

The patient had HER2-positive and PD-L1-negative metastatic gastric adenocarcinoma with rapid progression after surgery and multiple trastuzumab plus chemotherapy treatments, and options were limited after conventional approaches.

What outcomes were reported after RC48 plus the PRaG-based regimen?

After two treatment cycles the patient demonstrated a positive response, with a progression-free survival time of 6.5 months.

Sep 21, 2026

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