A Phase I/II Clinical Trial of LBL-034 in Patients With Relapsed Refractory Multiple Myeloma

Study Overview
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Brief Summary
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This is a single-arm, open-label, multicenter, dose-escalation, and dose-expansion phase I/II clinical study to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and efficacy of LBL-034 in patients with R/R MM.

Detailed Description
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A multicenter, open-label, phase I/II clinical study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of LBL-034 in patients with relapsed/refractory multiple myeloma. This trial includes two parts: phase I and phase II study. The dose escalation and dose expansion studies for LBL-034 will be conducted in the phase I study to evaluate safety, tolerability and determine RP2D. The efficacy of LBL-034 in treatment of R/R MM will be evaluated in the phase II study. Phase II study includes 2 arms. This clinical trial will enroll 66-418 patients in Phase I and Phase II studies.

Official Title
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A Multicenter, Open-label, Phase I/II Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of LBL-034 in Patients With Relapsed/Refractory Multiple Myeloma

Conditions
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Relapsed/Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: LBL-034 for Injection


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has voluntarily agreed to participate by giving written informed consent for the trial; Age ≥ 18 years on day of signing the Informed Consent Form; Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Status Scale； Documented initial diagnosis of multiple myeloma according to IMWG diagnostic criteria ； Have a life expectancy of at least 12 weeks； Fertile men and women of childbearing age are willing to take effective contraceptive measures (including abstinence, intrauterine devices, hormonal contraception, and correct use of condoms) from the signing of the informed consent form to 6 months after the last dose of the investigational drug; women of childbearing age include premenopausal women and women who had menopause less than two years ago. Blood pregnancy test results must be negative for women of childbearing age within 7 days prior to the initial dose of the investigational drug. Exclusion Criteria: Subjects who underwent major organ surgery (excluding needle biopsy) or significant trauma within 4 weeks prior to the initial use of the investigational drug, or require elective surgery during the trial period; Use of immunomodulatory drugs within 14 days prior to the initial use of the investigational drug, including but not limited to thymosin, interleukin-2, and interferon； Systemic use of corticosteroidsor other immunosuppressants within 14 days prior to the initial use of the investigational drug;The following conditions are excluded: Treatment with topical, ocular, intra-articular, intranasal, and inhaled corticosteroids; short-term use of glucocorticoids for preventive therapy (e.g., to prevent contrast allergy); Central nervous system (CNS) involvement or clinical signs of meningeal involvement of MM； Subjects with an active infection that currently requires intravenous anti infective therapy; History of immunodeficiency, including positive HIV antibody test results; Pregnant or lactating women; The investigator's assessment that there may be other factors affecting compliance among participants or that some may not be suitable for inclusion 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-034<br>LBL-034 for Injection; Initial dose - MTD; Q2W | Drug: LBL-034 for Injection<br>* Initial dose - MTD; Q2W; intravenous infusion<br>* Other names: LBL-034;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR (including the rates of Strin-gent complete response(sCR),complete response (CR) ,Very good partial response(VGPR),and partial response (PR)), evaluated based on the 2016 IMWG criteria, refers to the percentage of study subjects who achieve a complete response or partial response. It was used to evaluate the efficacy of LBL-034 in Phase II 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). | 
| 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. It was used to evaluate the safety of LBL-034 in Phase I study . | The DLT observation period starts from the first dose to 4 weeks after the full dose first administration (including the step-up dosing period, if any). | 
| 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. It was used to evaluate the tolerability of LBL-034 in Phase I study . | The MTD observation period starts from the first dose to 4 weeks after the full dose first administration (including the step-up dosing period, if any). | 

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) | 
| Minimal Residual Disease (MRD) | MRD-negative rate: Refers to the percentage of subjects who achieve MRD negativity at any time point after the initial dose and before disease progression or the initiation of a new anti-tumor therapy. | 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) |