A Phase I/II Clinical Trial of LBL-033 in the Treatment of Advanced Malignant Tumors

Study Overview
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Brief Summary
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This trial is an open and multicenter phase I/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 I/II clinical trial of LBL-033 in the treatment of patients with advanced malignant tumors，which aims to evaluate the safety, tolerability, PK characteristics, immunogenicity, and effectiveness. The trial is divided into 2 parts: Phase 1 and Phase 2 Phase I study: Dose-escalation and PK expansion.The PK expansion study will be judged on the basis of dose escalation data. Phase II study: Dose expansion included 4 cohorts that required patients with MUC16-positive malignancies.Blood samples will be collected from all subjects in this trial. Phase I and Phase II studies are expected to recruit 113-468 patients

Official Title
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A Multicenter, Open Phase I/II Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of LBL-033 in the Treatment of Patients With Advanced Malignant Tumors.

Conditions
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Advanced Malignant Tumors

Intervention / Treatment
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* Drug: LBL-033 for 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 years old when signing the informed consent form; The Eastern Cooperative Oncology Group's physical status scoring standard (ECOG) is 0 1; The expected survival time is at least 12 weeks; According to the evaluation of RECIST 1.1 standard, the subjects enrolled have at least one measurable Target lesion; Subject has adequate organ and bone marrow function，Conforming to laboratory test results: Males with fertility and females of childbearing age are willing to take effective contraceptive measures From the signing of the informed consent form to within 6 months after the last administration of the trial drug (including abstinence, intrauterine device, various hormonal contraception, correct use of contraception 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; Patients with active infection and currently requiring intravenous anti-infective treatment； Those who have clinically uncontrollable pleural effusion, pericardial effusion , requiring repeated drainage or medical intervention; The patient has a Medical history of immunodeficiency, including HIV antibody positive； 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.

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: LBL-033<br>LBL-033 for Injection; Initial dose - MTD; Q2W | Drug: LBL-033 for Injection<br>* Initial dose - MTD; Q2W; intravenous infusion<br>* Other names: LBL-033;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicities（DLT） | DLT describes side effects of a drug or other treatment that are serious enough to prevent an increase in dose or level of that treatment. | At the end of Cycle 1（28 days after the first prespecified 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（28 days after the first prespecified dose） | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cmax | Maximum serum concentration | From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (30 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 | From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (30 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 | From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (30 days after drug withdrawal or before the start of new anti-tumor therapy | 
| Disease Control Rate(DCR） | Percentage of participants achieving CR and PR and stable disease (SD). | From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (30 days after drug withdrawal or before the start of new anti-tumor therapy | 
| Duration of Response(DOR） | The period from the participants first achieving CR or PR to disease progression. | From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (30 days after drug withdrawal or before the start of new anti-tumor therapy | 
| Objective Response Rate (ORR) | Objective Response Rate (complete response (CR) + partial response (PR)), as assessed by Response Evaluation Criteria in Solid Tumors (RECIST 1.1), refers to the percentage of study subjects who achieve a complete response or partial response. This Secondary Outcome Measure was used for efficacy observations in Phase I study | From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (30 days after drug withdrawal or before the start of new anti-tumor therapy. |