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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Liver Cancer, Esophageal Squamous Cell Carcinoma, Gastric Adenocarcinoma, Cervical Cancer, MSI-H Colorectal Cancer

Intervention / Treatment
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* Drug: JS004
* Drug: Toripalimab Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sign the informed consent form voluntarily; Patient (both sex) ≥ 18 and ≤70 years at the time of signing informed consent; Expected survival ≥ 3 months; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Patients with advanced solid tumors confirmed histologically or cytologically At least one measurable lesion as a target lesion (RECIST v1.1 criteria); Agree to provide tumor tissue samples (provide fresh biopsy samples before treatment as far as possible; The patient has good organ function as indicated by screening laboratory results 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; Good compliance and cooperated with the follow-up. Exclusion Criteria: 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); 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 Received immunotherapy (including antibody and cell therapy) within 4 weeks prior to 1st administration Received allogeneic hematopoietic stem cell transplantation or solid organ transplantation in the past; Central nervous system metastases and/or cancerous meningitis Have or are suspected of having active autoimmune diseases, including but not limited to systemic lupus erythematosus rheumatoid arthritis inflammatory bowel disease autoimmune hepatitis A large amount of hydrothorax or ascites or pericardial effusion with clinical symptoms or requiring symptomatic treatment; 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 Pulmonary disease: interstitial pneumonia, obstructive pulmonary disease and symptomatic bronchospasm; A positive result for human immunodeficiency virus (HIV) antibody test; Known active tuberculosis (TB). Live vaccine was administered within 4 weeks prior to 1st administration Major surgical procedures (as defined by the investigator, e.g., open biopsy, severe trauma, etc.) within 4 weeks prior to 1st administration Have a history of psychotropic drug abuse and unable to withdraw or have mental disorders; Pregnant or lactating woman; Known to be allergic to JS004 or toripalimab and its components; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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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 |
| --- | --- | --- |
| OS | Duration of Response | 2 years | 
| DOR | Duration of Response | 2 years | 
| DCR | Disease Control Rate | 2 years | 
| PFS | Progression-free survival | 2 years | 
| ORR | Overall Response Rate | 2 years | 
| TTR | Time to remission | 2 years | 
| TTP | time to progression | 2 years |