A Phase I Clinical Study of Recombinant Humanized Anti-BTLA Monoclonal Antibody (JS004) Injection Combined With Toripalimab Injection in Patients With Advanced Solid Tumors

A Phase I Clinical Study Evaluating the Safety, Tolerability,of Recombinant Humanized Anti-BTLA Monoclonal Antibody (JS004) Injection Combined Witht Oripalimab in Patients With Advanced Solid Tumors

This is an open-label phase I study to evaluate the safety, tolerability, and initial efficacy of JS004 injection combined with Toripalimab Injection in patients with advanced solid tumors who have failed standard therapy.

Study Overview

• Status: Terminated
• Conditions: Liver Cancer, Esophageal Squamous Cell Carcinoma, Gastric Adenocarcinoma, Cervical Cancer, MSI-H Colorectal Cancer
• Intervention / Treatment: Drug: JS004; Drug: Toripalimab Injection

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China
      • Chinese PLA General Hospital
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China
      • Chongqing University Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Sign the informed consent form voluntarily;
2. Patient (both sex) ≥ 18 and ≤70 years at the time of signing informed consent;
3. Expected survival ≥ 3 months;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
5. Patients with advanced solid tumors confirmed histologically or cytologically
6. At least one measurable lesion as a target lesion (RECIST v1.1 criteria);
7. Agree to provide tumor tissue samples (provide fresh biopsy samples before treatment as far as possible;
8. The patient has good organ function as indicated by screening laboratory results
9. Males of reproductive potential or females of childbearing potential must use effective contraceptive methods (such as oral contraceptives, intrauterine device or barrier method combined with spermicide) during the trial and continue contraception for 6 months after the end of treatment;
10. Good compliance and cooperated with the follow-up.

Exclusion Criteria:

1. Any malignancy other than the disease under study within the past 5 years, except for malignancies that can be expected to be cured after treatment (including but not limited to adequately treated thyroid cancer, carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ of the breast treated surgically with curative intent);
2. patients received systemic antitumor therapy (including chemotherapy, small-molecule targeted drug therapy, endocrine therapy, etc.) or local antitumor therapy within 4 weeks prior to 1st administration
3. Received immunotherapy (including antibody and cell therapy) within 4 weeks prior to 1st administration
4. Received allogeneic hematopoietic stem cell transplantation or solid organ transplantation in the past;
5. Central nervous system metastases and/or cancerous meningitis
6. Have or are suspected of having active autoimmune diseases, including but not limited to systemic lupus erythematosus rheumatoid arthritis inflammatory bowel disease autoimmune hepatitis
7. A large amount of hydrothorax or ascites or pericardial effusion with clinical symptoms or requiring symptomatic treatment;
8. Have serious cardiovascular and cerebrovascular diseases, such as poorly controlled hypertension (systolic blood pressure>140mmHg and/or diastolic pressure> 90mmHg) or pulmonary arterial hypertension; Unstable angina or had a myocardial infarction in the 6 months prior to study use and had coronary artery bypass grafting or stenting; Chronic heart failure with grade 2 heart function (NYHA); Degree above heart block; Left ventricular ejection fraction (LVEF)<50%; Cerebrovascular accident (CVA) or transient ischemic attack (TIA) occurred within 6 months prior to medication
9. Pulmonary disease: interstitial pneumonia, obstructive pulmonary disease and symptomatic bronchospasm;
10. A positive result for human immunodeficiency virus (HIV) antibody test;
11. Known active tuberculosis (TB).
12. Live vaccine was administered within 4 weeks prior to 1st administration
13. Major surgical procedures (as defined by the investigator, e.g., open biopsy, severe trauma, etc.) within 4 weeks prior to 1st administration
14. Have a history of psychotropic drug abuse and unable to withdraw or have mental disorders;
15. Pregnant or lactating woman;
16. Known to be allergic to JS004 or toripalimab and its components;
17. Other severe, acute or chronic medical or psychiatric disorders or laboratory abnormalities that, in the investigator's opinion, may increase the risk associated with study participation or may interfere with the interpretation of study results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: JS004 200 mg in combination with Toripalimab Injection 240 mg was administered every 3 weeks	Drug: JS004; Usage and dosage: Inject 200mg once every 3 weeks; Drug: Toripalimab Injection; Usage and dosage: Inject 240mg once every 3 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of adverse events (AE) and serious adverse events (SAE) were assessed	Incidence and severity of adverse events (AE) and serious adverse events (SAE) as assessed according to NCI-CTCAE 5.0, as well as abnormalities in vital signs, electrocardiogram, and laboratory tests	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS	Progression-free survival	2 years
OS	Duration of Response	2 years
DOR	Duration of Response	2 years
DCR	Disease Control Rate	2 years
ORR	Overall Response Rate	2 years
TTR	Time to remission	2 years
TTP	time to progression	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Objective response rate based on iRECIST criteria (Version 2017);	2 years
DOR	duration of response based on iRECIST criteria (Version 2017);	2 years
DCR	disease control rate based on iRECIST criteria (Version 2017);	2 years
PFS	progression-free survival based on iRECIST criteria (Version 2017);	2 years

Collaborators and Investigators

• Sponsor: Shanghai Junshi Bioscience Co., Ltd.
• Collaborators: Sponsor GmbH

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2022
• Primary Completion (Actual): January 15, 2024
• Study Completion (Actual): January 15, 2024

Study Registration Dates

• First Submitted: June 5, 2022
• First Submitted That Met QC Criteria: June 16, 2022
• First Posted (Actual): June 22, 2022

Study Record Updates

• Last Update Posted (Estimated): December 3, 2025
• Last Update Submitted That Met QC Criteria: November 25, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Uterine Diseases; Genital Diseases, Female; Head and Neck Neoplasms; Liver Diseases; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Genital Neoplasms, Female; Carcinoma; Neoplasms, Squamous Cell; Uterine Cervical Diseases; Uterine Neoplasms; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Liver Neoplasms; Uterine Cervical Neoplasms; toripalimab
• Other Study ID Numbers: JS004-005-I

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