A Phase Ib/II Clinical Trial of LBL-007 Combined With Tislelizumab in the Treatment of Malignant Tumors

Study Overview
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Brief Summary
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This trial is an open and multicenter phase Ib/II clinical study, which aims to evaluate the safety, tolerability, PK characteristics, immunogenicity, and effectiveness.

Detailed Description
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This is an open, multicenter Phase Ib/II clinical trial of LBL-007 combined with Tislelizumab in the treatment of malignant tumors，which aims to evaluate the safety, tolerability, PK characteristics, immunogenicity, and effectiveness. The study was divided into two phases: Phase Ib (Part A): Dose escalation and PK expansion; Phase II includes: Part B, Part C, Part D, Part E, Part F, Part G, Part H. Part B   Part H will be designed and conducted based on the safety , tolerability and PK analysis of the Part A Study Part, after RP2D is determined, will be used for Part B   Part H cohort. Approximately 250-490 subjects will be enrolled (Specific sample size shall be subject to actual occurrence)

Official Title
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A Multicenter Phase Ib/II Clinical Study to Evaluate the Safety, Tolerability, and Efficacy of LBL-007 in Combination With Tislelizumab in the Treatment of Malignancies

Conditions
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Malignant Tumors

Intervention / Treatment
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* Drug: LBL-007 Injection
* Drug: Tislelizumab Injection
* Drug: Cisplatin Injection
* Drug: Gemcitabine Hydrochloride for Injection
* Drug: Docetaxel injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Agree to follow the experimental treatment plan and visit plan, join the group voluntarily, and sign a written informed consent form; Age ≥ 18 and ≤ 75 years old when signing the informed consent form, regardless of gender; The Eastern Cooperative Oncology Group's physical status scoring standard (ECOG) PS is 0 1; The expected survival time is at least 12 weeks; According to the evaluation criteria for the efficacy of solid tumors (RECIST 1.1), the subjects enrolled have at least one measurable tumor lesion; Subject has adequate organ and bone marrow function Males with fertility and females of childbearing age are willing to take effective contraceptive measures (including abstinence, intrauterine device, various hormonal contraception, correct use of contraception from the signing of the informed consent form to 6 months after the last administration of the trial drug Sets, etc.); women of childbearing age include pre-menopausal women and women within 2 years after menopause. Women of childbearing age must have a negative pregnancy test within 7 days before the first trial drug is administered. Exclusion Criteria: Have received other unmarketed clinical research drugs or treatments within 4 weeks before using the research drug for the first time; Those who have clinically uncontrollable pleural effusion, pericardial effusion or ascites, requiring repeated drainage or medical intervention; Women during pregnancy or lactation; The investigator believes that the subject has other conditions that may affect compliance or are not suitable for participating in this study. Patients with history of severe cardiovascular and cerebrovascular diseases. Patients with active infection and currently requiring intravenous anti-infective treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: LBL-007 & Tislelizumab<br>LBL-007 Injection; dose A or dose B; Q3W | Drug: LBL-007 Injection<br>* Initial dose - MTD; Q3W; intravenous infusion<br>* Other names: LBL-007;Drug: Tislelizumab Injection<br>* Initial dose; Q3W; intravenous infusion<br>* Other names: Tislelizumab;Drug: Cisplatin Injection<br>* Initial dose；Q3W; intravenous infusion<br>* Other names: Cisplatin;Drug: Gemcitabine Hydrochloride for Injection<br>* Initial dose；Q3W; intravenous infusion<br>* Other names: Gemcitabine Hydrochloride;Drug: Docetaxel injection<br>* Initial dose；Q3W; intravenous infusion<br>* Other names: Docetaxel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR (complete response (CR) + partial response (PR)), as assessed by Response Evaluation Criteria in Solid Tumors (RECIST), refers to the percentage of study subjects who achieve a complete response or partial response | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (30+7 days after drug withdrawal or before the start of new anti-tumor therapy | 
| Dose-limiting toxicities（DLT） | DLT is defined as toxicity during the DLT observation period (3 weeks after the first dose). | DLT is defined as toxicity during the DLT observation period. The duration of DLT observation period is from the first dose to 3 weeks after the first dose | 
| Maximum tolerated dose (MTD) | MTD is defined as the hightest dose level at which no more than 1 out of 6 subjects experiences a DLT during the first cycles | At the end of Cycle 1 (each cycle is 21days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum serum concentration | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (30+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| immunogenicity | The immunogenicity is evaluated by the incidence of anti-drug antibodies (ADA) and neutralizing antibodies (if applicable) in subjects | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (30+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| Disease Control Rate(DCR) | DCR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD). | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (30+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| Duration of Response(DOR) | To measure duration of response | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (30+7 days after drug withdrawal or before the start of new anti-tumor therapy) | 
| Tmax | After taking a single dose, Time to reach maximum plasma concentration | All subjects signed the informed consent form to the completion of the follow-up period of drug withdrawal (30+7 days after drug withdrawal or before the start of new anti-tumor therapy) |