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Denikitug（GS-1811）单独或联合Nivolumab或化疗用于治疗成人转移性胃癌、胃食管结合部腺癌和食管腺癌的研究

2026年11月5日 更新者：Gilead Sciences

一项2期、开放标签、多中心、随机研究，评估德尼奇图单药或联合纳武利尤单抗/化疗治疗HER2阴性、不可切除、复发和/或转移性胃腺癌、胃食管结合部（GEJ）腺癌及食管腺癌患者

The goal of this clinical study is to learn more about the study drug, Denikitug (DEN, GS-1811), to evaluate the efficacy and safety of Denikitug Monotherapy and Denikitug-based combinations in in participants with human epidermal growth factor receptor 2 (HER2)-Negative, unresectable, recurrent, and/or metastatic, gastroesophageal junction (GEJ), and esophageal adenocarcinomas.

The primary objective of this study is to assess the effect of DEN as a monotherapy or in combination with nivolumab (NIVO) or ramucirumab (RAM) and paclitaxel (PAC) on objective response rate (ORR) as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST Version1.1).

研究概览

地位

主动，不招人

条件

干预/治疗

研究类型

介入性

注册 (估计的)

120

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。

学习地点

  • 法国
      • Lyon、法国、69008
        • Centre Leon Berard, department of medical oncology
      • Marseille、法国、13009
        • Institut Paoli-Calmettes, department of medical oncology
  • 澳大利亚
    • New South Wales
      • Camperdown、New South Wales、澳大利亚、2050
        • Chris O'Brien Lifehouse
      • St Leonards、New South Wales、澳大利亚、2065
        • Royal North Shore Hospital
    • Queensland
      • Herston、Queensland、澳大利亚、4029
        • Royal Brisbane and Women's Hospital
    • South Australia
      • Bedford Park、South Australia、澳大利亚、5042
        • Flinders Medical Centre
    • Western Australia
      • Nedlands、Western Australia、澳大利亚、6009
        • Hollywood Private Hospital
  • 美国
    • Massachusetts
      • Boston、Massachusetts、美国、02114
        • Massachusetts General Hospital
      • Boston、Massachusetts、美国、02215
        • Dana Farber Cancer Institute (DFCI)
    • New York
      • Albany、New York、美国、12206
        • New York Oncology Hematology
      • New York、New York、美国、10021
        • Weill Cornell Medicine - New York Presbyterian Hospital
  • 西班牙
      • Barcelona、西班牙、8035
        • Hospital Universitari Vall d'Hebron
      • Madrid、西班牙、28041
        • Hospital Universitario 12 de Octubre
      • Pamplona、西班牙、31008
        • Hospital Universitario de Navarra
      • Valencia、西班牙、46010
        • Hospital Clinico Universitario de Valencia
  • 韩国
      • Seoul、韩国、03830
        • Seoul National University Hospital

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

Key Inclusion Criteria:

  • Histologically or cytologically confirmed diagnosis of locally advanced, unresectable, or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma (EAC).

  • Human epidermal growth factor receptor 2 (HER2)-negative status, as determined by local assessment using a validated immunohistochemistry assay, in situ hybridization or other amplification testing.

  • Has had disease progression during or after first line of systemic therapy for advanced or metastatic gastric, GEJ, or EACs, which must have included at least one of the following:

    1. Platinum- and fluoropyrimidine-based chemotherapy.
    2. Therapy with an anti-programmed cell death protein 1 (PD1) or anti-programmed cell death ligand 1 (anti-PD-L1) monoclonal antibody (patients with PD-L1-positive tumors must have received prior PD-1/PD-L1-based therapy).
    3. Zolbetuximab or other Claudin-18 (CLDN18).2-targeted therapy, if indicated based on biomarker status.

  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.

  • Have adequate organ function.

  • Male individuals and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use methods of contraception.

Key Exclusion Criteria:

  • Active or history of autoimmune disease requiring systemic treatment within 2 years, inflammatory bowel disease (IBD) (Crohn's/ulcerative colitis), celiac disease, or noninfectious enteritis/colitis. (Physiologic hormone replacement not considered systemic treatment).
  • History or current noninfectious pneumonitis/interstitial lung disease, including radiation-induced pneumonitis requiring steroids or active/recurrent pneumonitis of any etiology.
  • Documented microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) disease by local polymerase chain reaction (PCR) (microsatellite status) and/or informed consent form (ICH) (mismatch repair (MMR)) assay
  • (For Part 2 only) Has known history of peripheral neuropathy ≥ Grade 2 (per National Cancer Institute(NCI)-Common Tenninology Criteria for Adverse Events (CTCAE) Version 5.0).
  • (For Part 2 only) Known coagulopathy that increases the risk of bleeding, bleeding diatheses. Any other Grade 3 or higher hemorrhage/bleeding event within 28 days prior to enrollment.

Prior/Concurrent Therapy or Clinical Study Experience

  • Prior treatment with DEN or other C-C chemokine receptor 8 (CCR8)-targeted agents.
  • Prior Lonsurf (trifluridine-tipiracil) or paclitaxel (PAC)-based regimens in the first-line setting for advanced/metastatic gastroesophageal adenocarcinoma.
  • Any systemic therapy (including investigational) targeting vascular endothelial growth factor (VEGF) or VEGF receptor (VEGFR) signaling pathways.
  • Anticancer biologic within 4 weeks, orchemotherapy, targeted small molecule, or radiation therapy within 2 weeks prior to enrollment with unresolved adverse events (AE)s (Grade >2). (Observational study participants are eligible).
  • Prior allogenic tissue/solid organ or stem cell transplantation. (Exception: corneal transplant not requiring systemic immunosuppression is allowed).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

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：Part 1: Arm A: DEN (Dose A) and NIVO

Participants will receive DEN Dose A as an IV infusion in combination with NIVO as an IV infusion.
药品：Denikitug

Administered Intravenously

其他名称：
  • GS-1811
药品：Nivolumab

Administered Intravenously
实验性的：Part 1: Arm B: DEN (Dose B) and NIVO

Participants will receive DEN Dose B as an IV infusion in combination with NIVO as an IV infusion.
药品：Denikitug

Administered Intravenously

其他名称：
  • GS-1811
药品：Nivolumab

Administered Intravenously
实验性的：Part 1: Arm C: DEN (Dose B)

Participants will receive DEN Dose B as an IV infusion.
药品：Denikitug

Administered Intravenously

其他名称：
  • GS-1811
实验性的：Part 2: Arm D: Safety Run-in (SRI) Cohort

Participants will receive DEN in combination with ramucirumab (RAM) and paclitaxel (PAC).

If dose for DEN is deemed safe during the SRI Cohort, the study will move forward into the Expansion Period.
药品：Denikitug

Administered Intravenously

其他名称：
  • GS-1811
药品：Ramucirumab

Administered Intravenously

药品：Paclitaxel

Administered Intravenously
实验性的：Part 2: Arm D: Expansion Cohort

If DEN dose is deemed safe in Arm D: SRI Cohort, participants will receive DEN at recommended dose as an IV infusion in combination with RAM and PAC.
药品：Denikitug

Administered Intravenously

其他名称：
  • GS-1811
药品：Ramucirumab

Administered Intravenously

药品：Paclitaxel

Administered Intravenously

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
Objective Response Rate (ORR)
大体时间：Up to 4 years

ORR is defined as the percentage of participants who have achieved complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST Version 1.1.
Up to 4 years

次要结果测量

结果测量
措施说明
大体时间
发生治疗期不良事件（TEAEs）的参与者百分比，根据美国国家癌症研究所（NCI）不良事件通用术语标准（CTCAE）5.0版评定
大体时间：末次给药后首剂日期不超过120天，最多4年
末次给药后首剂日期不超过120天，最多4年
根据NCI CTCAE v5.0标准，报告临床实验室检查异常的参与者百分比
大体时间：末次给药后120天之内首次给药日期，最长4年。
末次给药后120天之内首次给药日期，最长4年。
药代动力学（PK）参数：DEN血清浓度
大体时间：长达4年
长达4年
出现针对Denikitug的治疗引发性抗药物抗体（ADA）的参与者百分比
大体时间：最长4年
最长4年
Duration of Response (DOR)
大体时间：Up to 4 years

DOR is defined as the time of first response CR or PR as assessed by investigator, per RECIST Version 1.1 until the date of first documented progressive disease (PD) or death, whichever comes first.
Up to 4 years
Progression-Free Survival (PFS)
大体时间：Up to 4 years

PFS is defined as the time from date of first dose until PD or death from any cause, whichever comes first as assessed by the investigator according to RECIST Version 1.1.
Up to 4 years
Overall Survival (OS)
大体时间：Up to 4 years

OS is defined as the length of time from first dose until the date of death from any cause.
Up to 4 years
PK Parameter: Cmax for Denikitug
大体时间：Up to 4 years

Cmax is defined as the maximum observed concentration.
Up to 4 years
PK Parameter: AUCall for Denikitug
大体时间：Up to 4 years

AUCall is defined as the cumulative areas under the curve for all time points.
Up to 4 years

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

Gilead Sciences

调查人员

  • 研究主任：Gilead Study Director、Gilead Sciences

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

有用的网址

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 (实际的)

2026年8月7日

初级完成 (估计的)

2030年1月1日

研究完成 (估计的)

2030年1月1日

研究注册日期

首次提交

2026年4月17日

首先提交符合 QC 标准的

2026年4月17日

首次发布 (实际的)

2026年4月23日

研究记录更新

最后更新发布 (实际的)

2026年11月10日

上次提交的符合 QC 标准的更新

2026年11月5日

最后验证

2026年11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

  • GS-US-742-7757
  • 2025-524095-27 (其他标识符：EU Trial (CTIS) Number)
  • 2025 (美国 NIH 拨款/合同)
  • CTR20263204 (其他标识符：China's Center for Drug Evaluation)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

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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