Study of JS004 Combined With Toripalimab for Advanced Lung Cancer

Study Overview
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Brief Summary
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This is an open-label phase I/II study to evaluate the safety, tolerability, pharmacokinetics and initial efficacy of JS004 injection combined with toripalimab in patients with advanced lung cancer who have failed standard therapy.

Official Title
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A Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Initial Efficacy of Recombinant Humanized Anti-BTLA Monoclonal Antibody (JS004) Injection Combined With Toripalimab in Patients With Advanced Lung Cancer

Conditions
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Advanced Lung Cancer

Intervention / Treatment
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* Drug: JS004 in combination with toripalimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria： Sign the informed consent form voluntarily; Patient (both sex) ≥ 18 years at the time of signing informed consent; Expected survival ≥ 3 months; Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; Extensive-stage small cell lung cancer (ES-SCLC, according to the Veterans Administration Lung Study Group VALG Staging) or/and locally advanced (stage IIIB/IIIC), metastatic or recurrent (stage IV) non-small cell lung cancer (NSCLC) by pathologically confirmed 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; provide archived samples within 2 years for patients who cannot provide fresh biopsy samples before treatment; The subject 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 previously treated with anti-BTLA or anti-HVEM antibodies; Patients previously discontinued treatment due to PD-1/PD-L1 inhibitor toxicity; Any adverse reactions caused by previous treatments have not recovered to CTCAE v5.0 Grade 1 or below (except alopecia and neurotoxicity, which cannot be recovered due to long-term presence as judged by the investigator); Received allogeneic hematopoietic stem cell transplantation or solid organ transplantation in the past; A large amount of hydrothorax or ascites or pericardial effusion with clinical symptoms or requiring symptomatic treatment; Pulmonary disease: interstitial pneumonia, obstructive pulmonary disease and symptomatic bronchospasm; Active infection requiring systemic therapy; A positive result for human immunodeficiency virus (HIV) antibody test; Known active tuberculosis (TB). For patients with suspicion of active TB should perform the test of chest X-ray, sputum, clinical signs and symptoms to exclude. 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

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JS004 200 mg in combination with toripalimab 240 mg was administered every 3 weeks as planned<br> | Drug: JS004 in combination with toripalimab<br>* Usage and dosage: Inject 200mg 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 | 
| Cmax | Maximum Plasma Concentration | 2 years | 
| Tmax | Time to Cmax | 2 years | 
| AUC0-t | Area under the concentration versus time curve from time 0 to the last measurable concentration | 2 years | 
| AUC0-inf | AUC from time 0 to infinity | 2 years | 
| Kel | Elimination rate constant | 2 years | 
| t1/2 | Elimination half life time | 2 years | 
| CL/F | Clearance | 2 years | 
| Vd/F | Apparent volume of distribution | 2 years | 
| Rac | Accumulation factor | 2 years |