JS107 versus doctor‑chosen therapy for CLDN18.2‑positive advanced stomach or gastroesophageal junction cancer after first‑line treatment

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

This trial tests whether JS107 works better than doctor‑selected chemotherapy for adults with CLDN18.2‑positive, HER2‑negative advanced stomach or gastroesophageal junction cancer who have already had at least one prior systemic therapy.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 560 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai Junshi Bioscience Co., Ltd. (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone
• Locations: 68 sites (Hefei, Anhui and 67 other locations)
• Trial ID: NCT07284134 on ClinicalTrials.gov

What this trial studies

This is a randomized, open‑label Phase 3 trial that will enroll about 560 patients with CLDN18.2‑positive, HER2‑negative locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma who progressed after at least one prior systemic therapy. Participants are randomized 1:1 to receive JS107 or investigator‑selected chemotherapy (examples include irinotecan, paclitaxel, or docetaxel). CLDN18.2 positivity must be confirmed by central immunohistochemistry on available tumor tissue before randomization, and key eligibility includes ECOG 0–1 and at least one measurable lesion per RECIST v1.1. The co‑primary endpoints are blinded independent central review (BICR) progression‑free survival and overall survival, with safety monitored throughout.

Who should consider this trial

Good fit: Adults (≥18) with HER2‑negative, CLDN18.2‑positive locally advanced or metastatic gastric/GEJ adenocarcinoma who progressed after at least one prior systemic therapy including fluorouracil and platinum, have ECOG 0–1, and at least one measurable lesion.

Not a fit: Patients who are CLDN18.2‑negative, HER2‑positive, have poor performance status, unresolved high‑grade toxicities from prior therapy, or cannot provide required tumor tissue are unlikely to benefit from enrollment.

Why it matters

Potential benefit: If successful, JS107 could provide a targeted treatment option that prolongs progression‑free and overall survival for CLDN18.2‑positive patients.

How similar studies have performed: Other agents targeting CLDN18.2 (for example zolbetuximab) have shown positive phase II/III results, supporting the promise of this targeted approach although JS107 itself remains investigational.

Eligibility criteria

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.

Where this trial is running

Hefei, Anhui and 67 other locations

• AnHui Provincial Cancer Hospital — Hefei, Anhui, China (Not_yet_recruiting)
• Peking University First Hospital — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Beijing Friendship Hospital, Capital Medical University — Beijing, Beijing Municipality, China (Not_yet_recruiting)
• Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital — Fuzhou, Fujian, China (Not_yet_recruiting)
• Union Hospital Affiliated to Fujian Medical University — Fuzhou, Fujian, China (Not_yet_recruiting)
• The First Hospital of Lanzhou University — Lanzhou, Gansu, China (Not_yet_recruiting)
• Gansu Provincial Cancer Hospital — Lanzhou, Gansu, China (Not_yet_recruiting)
• Gansu wuwei tumor hospital — Wuwei, Gansu, China (Not_yet_recruiting)
• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Nanfang hospital — Guangzhou, Guangdong, China (Not_yet_recruiting)
• The sixth affiliated hospital sun yat-sen university — Guangzhou, Guangdong, China (Not_yet_recruiting)
• Meizhou People's Hospital（Huangtang Hospital） — Meizhou, Guangdong, China (Not_yet_recruiting)
• Cancer Hospital of Shantou University Medical College — Shantou, Guangdong, China (Recruiting)
• Cancer Hospital Affiliated to Guangxi Medical University — Nanning, Guangxi, China (Not_yet_recruiting)
• People's Hospital of Guangxi Zhuang Autonomous Region — Nanning, Guangxi, China (Not_yet_recruiting)
• Cancer Hospital Chinese Academy of Medical Sciences Langfang Campus — Langfang, Hebei, China (Not_yet_recruiting)
• The Fourth Hospital of Hebei Medical University — Shijiazhuang, Hebei, China (Not_yet_recruiting)
• Affiliated Hospital of North China University of Technology — Tangshan, Hebei, China (Not_yet_recruiting)
• Harbin Medical University Cancer Hospital — Harbin, Heilongjiang, China (Not_yet_recruiting)
• Anyang Tumor Hospital — Anyang, Henan, China (Not_yet_recruiting)
• The First Affiliated Hospital of Henan University of Science & Technology — Luoyang, Henan, China (Not_yet_recruiting)
• Nanyang First People's Hospital National Third Class A Hospltal — Nanyang, Henan, China (Not_yet_recruiting)
• Puyang People's Hospital — Puyang, Henan, China (Not_yet_recruiting)
• Sanmenxia Central Hospital — Sanmenxia, Henan, China (Not_yet_recruiting)
• Henan Cancer Hospital — Zhengzhou, Henan, China (Not_yet_recruiting)
• The First Affiliated Hospital of Zhengzhouuniversity — Zhengzhou, Henan, China (Not_yet_recruiting)
• Zhoukou Central Hospital — Zhoukou, Henan, China (Recruiting)
• Tongji Hospital, Tongji Medical College, Huazhong University — Wuhan, Hubei, China (Not_yet_recruiting)
• Union Hospital Tongji Medical College Huazhong University of Science and Technology — Wuhan, Hubei, China (Not_yet_recruiting)
• Hubei Cancer Hospital — Wuhan, Hubei, China (Not_yet_recruiting)
• Xiangyang Cancer Hospital — Xiangyang, Hubei, China (Not_yet_recruiting)
• Yichang Central People's Hospital — Yichang, Hubei, China (Not_yet_recruiting)
• Xiangya Hospital of Central South University — Changsha, Hunan, China (Not_yet_recruiting)
• Hunan Cancer Hospital — Changsha, Hunan, China (Not_yet_recruiting)
• Baotou Tumor Hospital — Baotou, Inner Mongolia, China (Not_yet_recruiting)
• Jiangsu Province Hospital — Nanjing, Jiangsu, China (Not_yet_recruiting)
• Affiliated Hospital Of Jiangnan University — Wuxi, Jiangsu, China (Not_yet_recruiting)
• Xuzhou Central Hospital — Xuzhou, Jiangsu, China (Not_yet_recruiting)
• Northern Jiangsu People's Hospital — Yangzhou, Jiangsu, China (Not_yet_recruiting)
• Jiangxi Cancer Hospital (Jiangxi Second People's Hospital) — Nanchang, Jiangxi, China (Not_yet_recruiting)
• The First Affiliated Hospital of Nanchang University — Nanchang, Jiangxi, China (Not_yet_recruiting)
• The Third Bethune Hospital Of Jilin University — Changchun, Jilin, China (Not_yet_recruiting)
• Shengjing Hospital 0f China Medical University — Shenyang, Liaoning, China (Not_yet_recruiting)
• Liaoning Cancer Hospital&Institute — Shenyang, Liaoning, China (Not_yet_recruiting)
• General Hospital of Ningxia Medical university — Yinchuan, Ningxia, China (Not_yet_recruiting)
• Binzhou Medical University Hospital — Binzhou, Shandong, China (Not_yet_recruiting)
• Shandong Provincial Hospital — Ji'nan, Shandong, China (Not_yet_recruiting)
• Shandong First Medical University Affiliated Tumor Hospital — Jinan, Shandong, China (Not_yet_recruiting)
• Linyi Cancer Hospital — Linyi, Shandong, China (Not_yet_recruiting)
• Linyi People's Hospital — Linyi, Shandong, China (Not_yet_recruiting)

Study contacts

• Study coordinator: Yongdong Zhang

Conditions Advanced Gastric or Gastroesophageal Junction Adenocarcinoma