JS107 vs Investigator's Choice as Second-line or Later Therapy for Advanced CLDN18.2-Positive Gastricor GEJ Adenocarcinoma.

January 21, 2026 updated by: Shanghai Junshi Bioscience Co., Ltd.

This is a multicenter, randomized, controlled, open-label, Phase III study, designed to evaluate the efficacy and safety of JS107 versus investigator-selected therapy in the second-line or later treatment of patients with advanced gastric or gastroesophageal junction adenocarcinoma positive for CLDN18.2.

The study population consists of patients with CLDN18.2-positive, HER2-negative, locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma who have received at least one prior line of systemic therapy. The primary endpoints of the study are BICR-assessed progression-free survival and overall survival.

Number of subjects and allocation:This study plans to enroll approximately 560 subjects, who will be randomized in a 1:1 ratio to receive either JS107 (experimental group) or investigator-selected therapy (control group).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Patients with HER2 negative G/GEJ adenocarcinoma confirmed by histology/cytology. who have received at one prior line of systemic treatment and developed PD, and the previous treatment must include fluorouracil and platinum; CLDN18.2-positive, HER2-negative.

Study Type

Interventional

Enrollment (Estimated)

560

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Anhui
      • Hefei, Anhui, China, 230031
        • Not yet recruiting
        • Anhui Provincial Cancer Hospital
        • Contact:
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100034
        • Not yet recruiting
        • Peking University First Hospital
        • Contact:
      • Beijing, Beijing Municipality, China, 100050
        • Not yet recruiting
        • Beijing Friendship Hospital, Capital Medical University
        • Contact:
    • Fujian
      • Fuzhou, Fujian, China, 350014
        • Not yet recruiting
        • Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital
        • Contact:
      • Fuzhou, Fujian, China, 365110
        • Not yet recruiting
        • Union Hospital Affiliated to Fujian Medical University
        • Contact:
    • Gansu
      • Lanzhou, Gansu, China, 730000
        • Not yet recruiting
        • The First Hospital of Lanzhou University
        • Contact:
      • Lanzhou, Gansu, China, 730050
        • Not yet recruiting
        • Gansu Provincial Cancer Hospital
        • Contact:
      • Wuwei, Gansu, China, 733000
        • Not yet recruiting
        • Gansu Wuwei Tumor Hospital
        • Contact:
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • Not yet recruiting
        • Sun Yat-Sen University Cancer Center
        • Principal Investigator:
          • Ruihua Xu, Doctor
        • Contact:
      • Guangzhou, Guangdong, China, 510515
        • Not yet recruiting
        • Nanfang Hospital
        • Contact:
      • Guangzhou, Guangdong, China, 510655
        • Not yet recruiting
        • The Sixth Affiliated Hospital Sun Yat-sen University
        • Contact:
      • Meizhou, Guangdong, China, 514031
        • Not yet recruiting
        • Meizhou People's Hospital(Huangtang Hospital)
        • Contact:
      • Shantou, Guangdong, China, 515041
        • Recruiting
        • Cancer Hospital of Shantou University Medical College
        • Contact:
    • Guangxi
      • Nanning, Guangxi, China, 530000
        • Not yet recruiting
        • Cancer Hospital Affiliated to Guangxi Medical University
        • Contact:
      • Nanning, Guangxi, China, 530000
        • Not yet recruiting
        • People's Hospital of Guangxi Zhuang Autonomous Region
        • Contact:
    • Hebei
      • Langfang, Hebei, China, 065001
        • Not yet recruiting
        • Cancer Hospital Chinese Academy of Medical Sciences Langfang Campus
        • Contact:
      • Shijiazhuang, Hebei, China, 050011
        • Not yet recruiting
        • The Fourth Hospital of Hebei Medical University
        • Contact:
      • Tangshan, Hebei, China, 063000
        • Not yet recruiting
        • Affiliated Hospital of North China University of Technology
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150081
        • Not yet recruiting
        • Harbin Medical University Cancer Hospital
        • Contact:
    • Henan
      • Anyang, Henan, China, 455000
      • Luoyang, Henan, China, 471003
        • Not yet recruiting
        • The First Affiliated Hospital of Henan University of Science & Technology
        • Contact:
      • Nanyang, Henan, China, 473010
        • Not yet recruiting
        • Nanyang First People's Hospital National Third Class A Hospltal
        • Contact:
      • Puyang, Henan, China, 457100
        • Not yet recruiting
        • Puyang People's Hospital
        • Contact:
      • Sanmenxia, Henan, China, 472099
        • Not yet recruiting
        • Sanmenxia Central Hospital
        • Contact:
      • Zhengzhou, Henan, China, 450008
        • Not yet recruiting
        • Henan Cancer Hospital
        • Contact:
      • Zhengzhou, Henan, China, 450052
        • Not yet recruiting
        • The First Affiliated Hospital of Zhengzhouuniversity
        • Contact:
      • Zhoukou, Henan, China, 466099
    • Hubei
      • Wuhan, Hubei, China, 430079
        • Not yet recruiting
        • Hubei Cancer Hospital
        • Contact:
      • Wuhan, Hubei, China, 430000
        • Not yet recruiting
        • Tongji Hospital, Tongji Medical College, Huazhong University
        • Contact:
      • Wuhan, Hubei, China, 430040
        • Not yet recruiting
        • Union Hospital Tongji Medical College Huazhong University of Science and Technology
        • Contact:
      • Xiangyang, Hubei, China, 441199
        • Not yet recruiting
        • Xiangyang Cancer Hospital
        • Contact:
      • Yichang, Hubei, China, 443003
    • Hunan
      • Changsha, Hunan, China, 410013
      • Changsha, Hunan, China, 410008
        • Not yet recruiting
        • Xiangya Hospital of Central South University
        • Contact:
    • Inner Mongolia
      • Baotou, Inner Mongolia, China, 014030
        • Not yet recruiting
        • Baotou Tumor Hospital
        • Contact:
    • Jiangsu
      • Nanjing, Jiangsu, China, 210029
        • Not yet recruiting
        • Jiangsu Province Hospital
        • Contact:
      • Wuxi, Jiangsu, China, 214122
        • Not yet recruiting
        • Affiliated Hospital of Jiangnan University
        • Contact:
      • Xuzhou, Jiangsu, China, 221111
        • Not yet recruiting
        • Xuzhou Central Hospital
        • Contact:
      • Yangzhou, Jiangsu, China, 225001
        • Not yet recruiting
        • Northern Jiangsu People's Hospital
        • Contact:
    • Jiangxi
      • Nanchang, Jiangxi, China, 330209
        • Not yet recruiting
        • The First Affiliated Hospital Of Nanchang University
        • Contact:
      • Nanchang, Jiangxi, China, 330029
        • Not yet recruiting
        • Jiangxi Cancer Hospital (Jiangxi Second People's Hospital)
        • Contact:
    • Jilin
      • Changchun, Jilin, China, 130033
        • Not yet recruiting
        • The Third Bethune hospital of Jilin University
        • Contact:
    • Liaoning
      • Shenyang, Liaoning, China, 110042
        • Not yet recruiting
        • LiaoNing Cancer Hospital&Institute
        • Contact:
      • Shenyang, Liaoning, China, 110004
        • Not yet recruiting
        • Shengjing Hospital 0f China Medical University
        • Contact:
    • Ningxia
      • Yinchuan, Ningxia, China, 750004
        • Not yet recruiting
        • General Hospital of Ningxia Medical University
        • Contact:
    • Shandong
      • Binzhou, Shandong, China, 256603
        • Not yet recruiting
        • Binzhou Medical University Hospital
        • Contact:
      • Ji'nan, Shandong, China, 250021
        • Not yet recruiting
        • Shandong Provincial Hospital
        • Contact:
      • Jinan, Shandong, China, 250117
        • Not yet recruiting
        • Shandong First Medical University Affiliated Tumor Hospital
        • Contact:
      • Linyi, Shandong, China, 276000
        • Not yet recruiting
        • Linyi Cancer Hospital
        • Contact:
      • Linyi, Shandong, China, 276034
        • Not yet recruiting
        • Linyi People's Hospital
        • Contact:
      • Qingdao, Shandong, China, 266075
        • Not yet recruiting
        • The Affiliated Hospital of Qingdao University
        • Contact:
      • Weifang, Shandong, China, 261000
        • Not yet recruiting
        • Weifang People's Hospital
        • Contact:
    • Shanghai Municipality
      • Shanghai, Shanghai Municipality, China, 200123
        • Not yet recruiting
        • Shanghai Gobroad Cancer Hospital China Pharmaceutical University
        • Contact:
    • Shanxi
      • Datong, Shanxi, China, 037046
        • Not yet recruiting
        • The Third People's Hospital of Datong
        • Contact:
      • Linfen, Shanxi, China, 041000
        • Not yet recruiting
        • Linfen Central Hospital
        • Contact:
      • Taiyuan, Shanxi, China, 030032
        • Not yet recruiting
        • Shanxi Bethune Hospital
        • Contact:
      • Taiyuan, Shanxi, China, 030013
        • Not yet recruiting
        • Shanxi Cancer Hospital
        • Contact:
      • Taiyuan, Shanxi, China, 030001
        • Not yet recruiting
        • First Hospital of Shanxi Medical University
        • Contact:
      • Xi’an, Shanxi, China, 710061
        • Not yet recruiting
        • The First Affiliated Hospital of Xi'an Jiao Tong University
        • Contact:
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • Not yet recruiting
        • West China Hospital, Sichuan University
        • Contact:
      • Suining, Sichuan, China, 629000
        • Not yet recruiting
        • Suining Central Hospital
        • Contact:
      • Yibin, Sichuan, China, 644002
        • Not yet recruiting
        • The Second People's Hospital of Yibin
        • Contact:
    • Xinjiang
      • Ürümqi, Xinjiang, China, 830000
        • Not yet recruiting
        • Xinjiang Medical University Affiliated Tumor Hospital
        • Contact:
    • Yunnan
      • Kunming, Yunnan, China, 650118
    • Zhejiang
      • Hangzhou, Zhejiang, China, 310009
        • Not yet recruiting
        • The Second Affiliated Hospital Zhejiang University School of Medicine
        • Contact:
      • Hangzhou, Zhejiang, China, 310003
        • Not yet recruiting
        • The First Affiliated Hospital, Zhejiang University School of Medicine
        • Contact:
      • Hangzhou, Zhejiang, China, 310014
        • Not yet recruiting
        • Zhejiang Provincial People'S Hospital People'S Hospital of Hangzhou Medicalcollege
        • Contact:
      • Wenzhou, Zhejiang, China, 325000
        • Not yet recruiting
        • The First Affiliated Hospital of Wenzhou Medical University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Voluntarily participate in this study, have ICF signed after sufficient informed consent, and have good compliance.
  2. Age ≥ 18 years, male or female.
  3. ECOG PS 0 or 1.
  4. Expected survival period≥ 3 months.
  5. Patients with HER2 negative G/GEJ adenocarcinoma confirmed by histology/cytology.
  6. Patients who have received at least one prior line of systemic treatments and developed PD, and the previous treatment must include fluorouracil and platinum.
  7. Fresh or archival tumor tissue (blocks of formalin-fixed, paraffin-embedded [FFPE] tissue or unstained FFPE tumor tissue sections) must be available and comfirmed CLDN18.2 positivity by for central laboratory through immunohistochemistry (IHC) before randomization.
  8. Having ≥ 1 measurable lesion according to RECIST v1.1 (per investigator assessment).
  9. Any AEs and/or complications caused by previous therapies including surgery or radiotherapy have been adequately resolved to Grade 0 or 1 (per NCI-CTCAE v5.0 criteria) or have been stabilized in the judgment of investigators.

Exclusion Criteria:

  1. Previous treatment with any drug or cellular therapy targeting CLDN18.2 (except CLDN18.2 monotarget monoclonal antibody).
  2. Previously treated with an ADC loaded with a tubulin inhibitor.
  3. Received strong CYP3A inhibitor or inducer within 2 weeks or 5 half-lives prior to randomization, whichever is longer.
  4. Use of chemotherapy, immunotherapy or other anti-tumor therapies or participation in other clinical trials within 3 weeks prior to randomization, or use of oral fluorouracil, small molecule targeted drugs or traditional Chinese medicine for gastric cancer within 2 weeks prior to randomization.
  5. Major surgery (requiring general anaesthesia and >24 hours of Hospitalisation) or other clincal trial drug treatment within 4 weeks prior to randomization, or radiotherapy within 2 weeks prior to randomization.
  6. Imaging demonstrating brain metastases (except patients who have completed whole brain radiotherapy or local therapy (such as surgery), have discontinued prednisone for at least 4 weeks prior to randomization, and have stable radiologically confirmed tumor lesions and no clinical symptoms of tumor during 4 weeks prior to randomization), metastases to meninges, or spinal cord compression.
  7. Tumor invades important surrounding structures (e.g., large blood vessels, trachea, etc.) with high risk of rupture and hemorrhage or airway fistula, or metastases to bone with high risk of paraplegia.
  8. Thromboembolic events within 3 months prior to randomization (except patients with non-pulmonary Thromboembolism who do not require treatment or have been stably treated with anticoagulants for 14 days or longer prior to randomization).
  9. History of other neoplasm malignant within 5 years prior to randomization, except for neoplasm malignant cured after treatment.
  10. Having active autoimmune diseases requiring systemic treatment (i.e., immunologic modulator, corticosteroid, or Immunosuppression) within 2 years prior to randomization; replacement therapy (such as thyroid hormone, Insulin, or physiologic corticosteroid replacement therapy due to adrenal or pituitary insufficiency) is not considered systemic treatment.
  11. Known severe allergic reaction to any component in the investigational drug formula.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Experimental group
JS107: 3mg/kg, intravenous infusion, on Day 1, with a treatment cycle of every 21 days.
Drug: JS107 for Injection
Subjects who are confirmed to meet the inclusion and exclusion criteria after screening will be randomly assigned in a 1:1 ratio to receive JS107 treatment (experimental group) or investigator's chosen treatment (control group) until the criteria for terminating the study treatment as specified in the protocol are met (including subjects experiencing BICR-confirmed radiological PD, death, loss to follow-up, withdrawal of informed consent, or termination of the study by the sponsor, whichever occurs first).
Active Comparator: Control group

Including 3 treatment regimens: irinotecan, paclitaxel, and docetaxel. investigators will select one regimen based on the patient's previous treatment medications, clinical benefits, and tolerability, and the administration will follow clinical guidelines and/or clinical practices. In addition, before administration, corresponding premedications (including antiemetics, preventive anti-allergy drugs, etc.) can be given with reference to clinical guidelines or drug instructions.

Irinotecan: 150mg/m², intravenous infusion, on days 1 and 15, with a 28-day treatment cycle.

Paclitaxel: 80mg/m², intravenous infusion, on days 1, 8, and 15, with a 28-day treatment cycle.

Docetaxel: 75mg/m², intravenous infusion, on day 1, with a 21-day treatment cycle.
Drug: Irinotecan
Subjects who are confirmed to meet the inclusion and exclusion criteria after screening will be randomly assigned in a 1:1 ratio to receive JS107 treatment (experimental group) or investigator's chosen treatment (control group) until the criteria for terminating the study treatment as specified in the protocol are met (including subjects experiencing BICR-confirmed radiological PD, death, loss to follow-up, withdrawal of informed consent, or termination of the study by the sponsor, whichever occurs first).
Drug: Paclitaxel
Subjects who are confirmed to meet the inclusion and exclusion criteria after screening will be randomly assigned in a 1:1 ratio to receive JS107 treatment (experimental group) or investigator's chosen treatment (control group) until the criteria for terminating the study treatment as specified in the protocol are met (including subjects experiencing BICR-confirmed radiological PD, death, loss to follow-up, withdrawal of informed consent, or termination of the study by the sponsor, whichever occurs first).
Drug: Docetaxel
Subjects who are confirmed to meet the inclusion and exclusion criteria after screening will be randomly assigned in a 1:1 ratio to receive JS107 treatment (experimental group) or investigator's chosen treatment (control group) until the criteria for terminating the study treatment as specified in the protocol are met (including subjects experiencing BICR-confirmed radiological PD, death, loss to follow-up, withdrawal of informed consent, or termination of the study by the sponsor, whichever occurs first).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
BICR-PFS
Time Frame: up to 2 years
Progression-Free Survival (BICR-PFS) evaluated based on Blinded Independent Central Review (BICR) (according to the RECIST v1.1 criteria)
up to 2 years
Overall Survival
Time Frame: up to 5 years
The primary endpoint of overall survival (OS) in this multicenter, randomized, open-label Phase III study is the time from randomization to death from any cause, aiming to compare the benefit between JS107 and investigator's choice of therapy in patients with CLDN18.2-positive, HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma who have received at least one prior line of systemic therapy.
up to 5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
INV-PFS
Time Frame: up to 2 years
Progression-Free Survival evaluated by investigators (INV-PFS, according to the RECIST v1.1 criteria)
up to 2 years
BICR-ORR or INV-ORR
Time Frame: up to 2 years
ORR evaluated by investigators or BICR (according to the RECIST v1.1 criteria)
up to 2 years
BICR-DCR or INV -DCR
Time Frame: up to 2 years
Progression-Free Survival evaluated by investigators (INV-PFS, according to the RECIST v1.1 criteria)
up to 2 years
BICR-DoR or INV -DoR
Time Frame: up to 2 years
DoR (based on the RECIST v1.1 criteria) evaluated by investigators or BICR
up to 2 years
The incidence rate and severity of AE
Time Frame: up to 2 years
The incidence and severity of adverse events (AEs) evaluated according to the NCI-CTC AE v5.0 standard
up to 2 years
Valley concentration of JS107
Time Frame: up to 2 years
Valley concentration of JS107 (including ADC, total antibody, and toxin)
up to 2 years
anti-drug antibodies (ADA) for JS107
Time Frame: up to 2 years
Incidence and titer of anti-drug antibodies (ADA) for JS107 (including ADC, total antibody, and toxin)
up to 2 years
Incidence of neutralizing antibodies (NAb) to JS107
Time Frame: up to 2 years
Incidence of neutralizing antibodies (NAb) to JS107 (including ADC, total antibody, and toxin)
up to 2 years

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
HRQOL
Time Frame: up to 2 years
HRQOL (based on FACT-Ga and EORTC QLQ-C30 questionnaires)
up to 2 years
expression levels of CLDN18.2
Time Frame: up to 2 years
Detect different expression levels of CLDN18.2 in tumor tissues and analyze the correlation with therapeutic efficacy
up to 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Junshi Bioscience Co., Ltd.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 24, 2025

Primary Completion (Estimated)

October 13, 2027

Study Completion (Estimated)

October 17, 2028

Study Registration Dates

First Submitted

December 3, 2025

First Submitted That Met QC Criteria

December 15, 2025

First Posted (Actual)

December 16, 2025

Study Record Updates

Last Update Posted (Actual)

January 22, 2026

Last Update Submitted That Met QC Criteria

January 21, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JS107-006-III-GC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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