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Retlirafusp Alfa or Adebrelimab Plus SOX as Neoadjuvant Therapy for HER2-Negative Resectable Gastric or Gastroesophageal Junction Adenocarcinoma

2026年11月3日 更新者：Qun Zhao

A Randomized, Exploratory Phase II Study of Retlirafusp Alfa or Adebrelimab Combined With SOX as Neoadjuvant Therapy for HER2-Negative Resectable Gastric or Gastroesophageal Junction Adenocarcinoma

This multicenter, randomized, open-label, exploratory phase II study aims to evaluate the efficacy and safety of perioperative Retlirafusp Alfa plus SOX versus adebrelimab plus SOX in adult patients with previously untreated, HER2-negative, resectable locally advanced gastric or gastroesophageal junction adenocarcinoma (clinical stage II-III, AJCC 8th edition).

Approximately 98 participants will be randomized at a 1:1 ratio via stratified block randomization. Stratification factors include tumor location (gastric versus gastroesophageal junction) and PD-L1 combined positive score (CPS <1 versus CPS ≥1).

Participants will receive 3 preoperative cycles of assigned immunotherapy combined with SOX, followed by D2 radical gastrectomy performed 4-8 weeks after the last neoadjuvant cycle. Postoperatively, participants will receive 5 cycles of the same immunotherapy plus SOX, then up to 9 cycles of immunotherapy monotherapy, with a maximum of 17 total immunotherapy cycles.

The primary outcome measure is pathologic complete response (pCR) rate. Secondary outcome measures include R0 resection rate, event-free survival, disease-free survival, overall survival, surgical safety, adverse events, laboratory abnormalities, and treatment tolerability.

研究概览

地位

尚未招聘

条件

干预/治疗

研究类型

介入性

注册 (估计的)

98

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria

  1. Voluntary signed written informed consent.

  2. Age ≥ 18 years.

  3. Histologically-confirmed gastric / gastroesophageal junction adenocarcinoma; Siewert II / III are eligible.

  4. Resectable clinical stage II-III (cT1-2N+M0, cT3-4aNanyM0, AJCC 8th edition) confirmed by CT / MRI.

  5. No prior anti-cancer therapy (surgery, radiotherapy, chemotherapy, targeted or immunotherapy).

  6. Investigator-assessable for R0 resection; planned curative surgery after neoadjuvant therapy.

  7. Able to swallow oral tablets.

  8. ECOG-PS 0-1.

  9. Available PD-L1 CPS result or 3-5 unstained tumor slides for testing (fresh or pre-randomization FFPE tissue acceptable).

  10. Estimated life expectancy ≥ 12 months.

  11. Adequate organ function (no transfusion / G-CSF in prior 14 d):

    • ANC ≥ 1.5 × 10⁹/L; platelets ≥ 80 × 10⁹/L; Hb ≥ 90 g/L
    • Total bilirubin < 1.5 × ULN; ALT/AST ≤ 2.5 × ULN
    • Serum Cr ≤ 1.5 × ULN or CrCl > 50 mL/min

  12. Women of child-bearing potential: negative serum pregnancy test ≤ 72 h pre-randomization; effective contraception (longer of 3 months post-last retlirafusp alfa / adebrelimab or 6 months post-chemotherapy). Fertile-partner males: surgical sterility or same contraception window; no sperm donation during study.

Exclusion Criteria

  1. Known HER2-positive tumor.
  2. Anticipated transthoracic surgical approach.
  3. Unresectable disease, surgical contraindication or refusal of surgery.
  4. Other malignancy within 5 years (exception: cured basal-cell skin, cervical / breast carcinoma-in-situ).
  5. Laparoscopy shows peritoneal metastasis, positive peritoneal cytology (CY1P0) or AJCC 8th T4b disease.
  6. Cardiac abnormalities: NYHA ≥ II heart failure or LVEF < 50 %; unstable angina; MI within 1 year; QTc prolongation (male>450 ms, female>470 ms); significant ECG abnormality / high-grade AV-block / PR>250 ms; risk factors for QTc prolongation.
  7. Gastrointestinal obstruction signs/symptoms within prior 6 months (except symptoms resolved by definitive surgery).
  8. Coagulopathy (INR>2.0, PT>16 s), bleeding diathesis or ongoing thrombolytic / anticoagulant therapy (prophylactic low-dose aspirin / LMWH allowed).
  9. Clinically-significant bleeding tendency within 3 months pre-randomization. Persistently positive fecal occult blood requires gastroscopy.
  10. GI perforation or fistula within prior 6 months.
  11. Arterial / venous thromboembolic event within prior 6 months (superficial phlebothrombosis excluded).
  12. Hereditary / acquired bleeding or thrombotic diathesis.
  13. Active ulcer, unhealed wound or fracture.
  14. Major vascular disease within prior 6 months.
  15. CTCAE>grade 2 severe infection within 4 weeks pre-randomization; active pulmonary inflammation; ongoing need for systemic antibiotics (≤48 h prophylactic IV antibiotics permitted).
  16. Active hepatitis B (HBsAg+ plus HBV-DNA ≥ 2000 IU/mL) or active hepatitis C.
  17. Congenital / acquired immunodeficiency including HIV infection.
  18. Prior or planned organ / allogeneic bone-marrow transplantation.
  19. Interstitial lung disease / pneumonitis (current or steroid-treated history); pulmonary fibrosis, pneumoconiosis, active tuberculosis or severe pulmonary impairment on screening CT.
  20. Active autoimmune disease or high-risk relapse history (exceptions: hormone-replaced hypothyroidism; controlled type 1 diabetes; stable vitiligo, psoriasis, resolved childhood asthma; asthma requiring bronchodilators is excluded).
  21. Systemic immunosuppressive corticosteroids (>10 mg prednisone-equivalent daily) within 7 days pre-randomization.
  22. Live-attenuated vaccine within 28 days pre-randomization or planned during-/within 60 days post-study-treatment.
  23. Hypersensitivity to any study drug or excipients.
  24. Investigational-drug clinical trial participation within prior 4 weeks.
  25. Pregnancy, lactation or planned pregnancy during study treatment.
  26. Investigator-judged other conditions interfering with study conduct or participant safety (substance abuse, severe psychiatric illness etc).

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Retlirafusp Alfa Plus SOX

Retlirafusp alfa plus SOX for 3 preoperative 21-day cycles, followed by D2 radical surgery, then retlirafusp alfa plus SOX for 5 postoperative cycles, followed by retlirafusp alfa alone for 9 cycles. Retlirafusp alfa may be given for a maximum of 17 cycles in total.
药品：Retlirafusp Alfa Plus Chemotherapy

1800 mg administered by intravenous infusion on Day 1 of each 21-day cycle. Given with SOX for 3 preoperative and 5 postoperative cycles, then as monotherapy for 9 cycles, up to 17 cycles in total. When administered with oxaliplatin, retlirafusp alfa is infused first, with an interval of at least 30 minutes before oxaliplatin.
实验性的：Adebrelimab Plus SOX

Adebrelimab plus SOX for 3 preoperative 21-day cycles, followed by D2 radical surgery, then adebrelimab plus SOX for 5 postoperative cycles, followed by adebrelimab alone for 9 cycles. Adebrelimab may be given for a maximum of 17 cycles in total.
药品：Adebrelimab Plus chemotherapy

1200 mg administered by intravenous infusion on Day 1 of each 21-day cycle. Given with SOX for 3 preoperative and 5 postoperative cycles, then as monotherapy for 9 cycles, up to 17 cycles in total. When administered with oxaliplatin, adebrelimab is infused first, with an interval of at least 30 minutes before oxaliplatin.

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Pathologic Complete Response (pCR) Rate
大体时间：After D2 radical surgery (within 8 weeks after neoadjuvant completion)

Proportion of participants achieving TRG0 (CAP criteria): no viable tumor cells in primary tumor and regional lymph nodes after neoadjuvant therapy. Evaluated on surgical resection specimen.
After D2 radical surgery (within 8 weeks after neoadjuvant completion)

次要结果测量

结果测量
措施说明
大体时间
R0 Resection Rate
大体时间：At the time of surgery.

Proportion of subjects achieving R0 resection evaluated by surgical-pathology report.
At the time of surgery.
Event-Free Survival(EFS)
大体时间：Up to 5 years from randomization.

Time from randomization to disease progression, recurrence or death from any cause (whichever occurs first).
Up to 5 years from randomization.
Disease-Free Survival(DFS)
大体时间：Up to 5 years after surgery.

For post-surgery subjects without residual disease: time from surgery to disease recurrence or death from any cause.
Up to 5 years after surgery.
Overall Survival(OS)
大体时间：Up to 5-year follow-up post-randomization.

Time from randomization to death from any cause.
Up to 5-year follow-up post-randomization.
Safety and Tolerability
大体时间：From first study drug dose to safety-follow-up completion (90 days after last immunotherapy or 30 days post-chemotherapy/surgery, whichever occurs later).

Incidence, severity (CTCAE v6.0) of adverse events(AE), serious adverse events(SAE); surgical-related complications; treatment-related dose modification/discontinuation rate.
From first study drug dose to safety-follow-up completion (90 days after last immunotherapy or 30 days post-chemotherapy/surgery, whichever occurs later).

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Qun Zhao

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年11月30日

初级完成 (估计的)

2029年3月30日

研究完成 (估计的)

2031年12月30日

研究注册日期

首次提交

2026年11月3日

首先提交符合 QC 标准的

2026年11月3日

首次发布 (实际的)

2026年11月9日

研究记录更新

最后更新发布 (实际的)

2026年11月9日

上次提交的符合 QC 标准的更新

2026年11月3日

最后验证

2026年10月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • MA-GC-II-033

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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