STUDY PROTOCOL article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1638316
This article is part of the Research TopicCommunity Series in Interaction of Cell Subtypes in Tumor Microenvironment, and Implications for Immunotherapy Volume IIView all articles
Fruquintinib and sintilimab plus SOX as perioperative therapy for locally resectable advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma : study protocol for a prospective, single-arm, phase II clinical trial
Provisionally accepted
- Liaoning Cancer Hospital, China Medical University, Shenyang, China
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Locally advanced gastric/gastroesophageal junction (G/GEJ) adenocarcinoma faces high recurrence risks despite radical surgery. Perioperative chemotherapy (e.g., FLOT regimen) improves survival but has limited pathological complete response (pCR) rates and significant toxicity. Immunotherapy and anti-angiogenic agents show promise in advanced G/GEJ cancer. This trial evaluates fruquintinib (a VEGFR-1/2/3 inhibitor), sintilimab (PD-1 inhibitor), and SOX (oxaliplatin+S-1) as perioperative therapy for resectable locally advanced G/GEJ adenocarcinoma.This prospective, single-arm, phase II trial (N = 25) enrolls treatment-naïve adults (18-75 years) with histologically confirmed, resectable cT3-4aN+M0 G/GEJ adenocarcinoma (AJCC 8th edition).Patients receive 3 cycles of neoadjuvant therapy:Fruquintinib:4 mg orally, days 1-14 (21-day cycle). S-1: 80-120 mg orally twice daily (based on BSA), days 1-14. Oxaliplatin: 130 mg/m² IV, day 1. Sintilimab: 200 mg IV, day 1.Radical gastrectomy with D2 lymphadenectomy follows 4-6 weeks post-neoadjuvant therapy. Adjuvant therapy (3 cycles of sintilimab for pCR patients; 3 cycles of preoperative regimen for non-pCR) starts 4-6 weeks post-surgery. Endpoints: Primary: pCR rate (ypT0/Tis ypN0 per CAP criteria). Secondary: R0 resection rate, major pathological response (MPR, ≤10% residual tumor), 2-year event-free survival (EFS), 2-year overall survival (OS), safety (NCI CTCAE v5.0). Exploratory: Biomarker analysis of tumor microenvironment.Statistical Analysis: Sample size (25 patients) was calculated using Fisher's exact test (one-sided α = 0.05, power = 80%), assuming pCR improvement from 5% (historical control) to 20%. Efficacy analyses use intention-to-treat (ITT) population; safety analyses include patients receiving ≥1 neoadjuvant dose.This is the first trial combining fruquintinib, sintilimab, and SOX in perioperative G/GEJ cancer. If successful, it may expand treatment options for locally advanced disease. Limitations include single-arm design and small sample size.
Keywords: G/GEJ adenocarcinoma, Perioperative treatment, fruquintinib, Sintilimab, effectiveness
Received: 30 May 2025; Accepted: 11 Jul 2025.
Copyright: © 2025 Meng, Yang, Liu, Wang, Yao and Zhang. This is an 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) or licensor 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.
* Correspondence: Xiangyu Meng, Liaoning Cancer Hospital, China Medical University, Shenyang, China
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