JS107 in Combination With Toripalimab and Chemotherapy for the Treatment of CLDN18.2-positive Gastric or Gastroesophageal Junction Adenocarcinoma

A Multicenter, Randomized, Controlled, Open-label Phase III Clinical Trial Evaluating the Efficacy and Safety of JS107 in Combination With Toripalimab and Chemotherapy Versus Sintilimab in Combination With Chemotherapy as First-line Treatment for CLDN18.2-positive Advanced Gastric or Gastroesophageal Junction Adenocarcinoma

This study is a multicenter, randomized, open-label, controlled Phase III clinical trial aimed at evaluating the efficacy and safety of JS107 combined with toripalimab XELOX versus sintilimab combined with XELOX as first-line treatment for patients with advanced G/GEJ adenocarcinoma.

The research subjects were patients with unresectable locally advanced, recurrent or metastatic G/GEJ adenocarcinoma who were CLDN18.2-positive and HER2-negative and had not received systemic treatment before (except for neoadjuvant/adjuvant therapy that occurred more than 6 months after disease progression/recurrence from the last treatment). The study took BICR-PFS and OS as Dual primary endpoints.

Study Overview

• Status: Not yet recruiting
• Conditions: Gastric Adenocarcinoma
• Intervention / Treatment: Drug: Injection JS107&Toripalimab& Oxaliplatin Injection& Capecitabine; Drug: Sintilimab& Oxaliplatin Injection& Capecitabine

• Study Type: Interventional
• Enrollment (Estimated): 600
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Bifeng Liu; Phone Number: 021-61058800; Email: bifeng_liu@junshipharma.com
• Study Contact Backup: Name: Junliang Li; Email: Junliang_li@junshipharma.com

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center
      • Contact: Ruihua Xu, PhD; Phone Number: 18758246502; Email: xurh@sysucc.org.cn
      • Principal Investigator: Ruihua Xu, Ph.D

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. The patient voluntarily participated, provided informed consent, signed a written informed consent form, and had good compliance.
2. Age ≥18 years (including), male and female. 3)Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 4）Expected survival period ≥3 months.

5）Patients with HER2-negative, unresectable locally advanced, recurrent, or Metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma confirmed by histology/cytology. 6）Previously untreated for systemic therapy for locally advanced, recurrent, or Metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. 7）Positive for CLDN18.2 by IHC testing at the central laboratory. 8）According to the RECIST v1.1 criteria, the patient has ≥1 measurable lesion. 9）The functional level of the organ meets the requirements of the protocol. 10）Agree to use contraception during the study period; females of reproductive potential will undergo a blood pregnancy test within 7 days prior to randomization, with a negative result.

Exclusion Criteria:

1. Previously received any drug or cell therapy targeting CLDN18.2
2. Received major surgery, live vaccine administration, or Drug therapy with other investigational medicinal products, or received radiotherapy within 2 weeks prior to randomization.
3. Imaging shows cerebral tumor lesions (unless whole-brain radiotherapy or surgery, etc., local treatment has been completed, and imaging and clinical stability have been assessed according to the protocol) 4)Peripheral neuropathy ≥ Grade 2

5）Idiopathic pulmonary fibrosis, Organising pneumonia, drug-induced pneumonia, idiopathic pneumonia, or evidence of active pneumonia on screening chest computerised tomography (CT) scan 6）Pericardial effusion, Pleural effusion, or ascites with a large volume, or with clinical symptoms, or requiring symptomatic treatment.

7）There is a need for systemic antimicrobial or antiviral therapy for active infection.

8）Subjects who cannot take oral medications, require enteral nutrition to maintain feeding, or have Malabsorption syndrome or other conditions affecting gastrointestinal Malabsorption.

9）Presence of biliary or gastrointestinal obstruction, or persistent recurrent vomiting 10）Weight loss of >10% within the previous 2 months or severe Malnutrition, known prior to randomization.

11）History of gastrointestinal perforation and/or fistula within the prior 6 months; presence of high-risk Haemorrhage of digestive tract disease or risk of rupture bleeding or gastrointestinal/respiratory fistula 12）Serious cardiovascular and cerebrovascular diseases 13）History of systemic treatment for autoimmune diseases within the past 2 years 14）Randomly selected patients with any other Neoplasm malignant within the past 5 years.

15）Known severe allergic reaction to any ingredient in the study drug formulation 16）Known active Hepatitis B, active Hepatitis C, human immunodeficiency (HIV) infection, or have undergone allogeneic stem cell or Solid organ transplant.

17）Diseases determined by researchers to be unsuitable for participation.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: JS107 in combination with Toripalimab and XELOX Chemotherapy	Drug: Injection JS107&Toripalimab& Oxaliplatin Injection& Capecitabine; JS107: 2 mg/kg on day 1 Q3W; Toripalimab (T): 240 mg on day 1 Q3W. Capecitabine (C): 750 mg/m² BID Day1-Day14, Q3W，Oxaliplatin 100mg/m² on Day1 Q3W, Maximum of 6 cycles.
Active Comparator: Sintilimab in combination with XELOX Chemotherapy	Drug: Sintilimab& Oxaliplatin Injection& Capecitabine; Sintilimab: 3 mg/kg or 200 mg Day1 Q3W, Capecitabine: 1000 mg/m² BID Day1-Day14, Q3W，Oxaliplatin 130mg/m² on Day1 Q3W, Maximum of 6 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
BICR-PFS	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	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	Progression-Free Survival evaluated by investigators (INV-PFS, according to the RECIST v1.1 criteria)	up to 2 years
BICR-ORR or INV-ORR	ORR evaluated by investigators or BICR (according to the RECIST v1.1 criteria)	up to 2 years
BICR-DCR or INV -DCR	Progression-Free Survival evaluated by investigators (INV-PFS, according to the RECIST v1.1 criteria)	up to 2 years
BICR-DoR or INV -DoR	DoR (based on the RECIST v1.1 criteria) evaluated by investigators or BICR	up to 2 years
The incidence rate and severity of AE	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	Valley concentration of JS107 (including ADC, total antibody, and toxin)	up to 2 years
Incidence of neutralizing antibodies (NAb) to JS107	Incidence of neutralizing antibodies (NAb) to JS107 (including ADC, total antibody, and toxin)	up to 2 years
Anti-drug antibodies (ADA) for JS107	Incidence and titer of anti-drug antibodies (ADA) for JS107 (including ADC, total antibody, and toxin)	up to 2 years
Blood trough concentration of toripalimab	To evaluate the blood trough concentration of toripalimab	up to 2 years
Immunogenicity of toripalimab	Incidence and titer of anti-drug antibody (ADA) of toripalimab,	up to 2 years
Incidence of neutralizing antibodies (NAb) to Toripalimab	ADA-positive samples for the presence of Neutralising antibodies (Nab).	up to 2 years

Collaborators and Investigators

• Sponsor: NingBo Junyan Hongshi Biosciences Co., Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): May 30, 2026
• Primary Completion (Estimated): January 31, 2029
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: May 7, 2026
• First Submitted That Met QC Criteria: May 7, 2026
• First Posted (Actual): May 13, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: JS107-004-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