Relapsed/Refractory Multiple Myeloma
Conditions
Brief summary
This trial is a single-arm, open-label, multicenter phase I/II clinical study of LBL-034 in patients with RRMM to evaluate the safety, tolerability, PK profile, immunogenicity and efficacy of LBL-034.
Detailed description
This trial includes two parts: Phase I study 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. In the dose escalation phase, the DLT observation period is from the first dose to 4 weeks after the prescribed dose is administered.Dose expansion or study at different dosing intervals in the expected effective dose group will be judged by the investigator and the sponsor based on the dose escalation data of LBL-034. The efficacy of LBL-034 in the treatment of RRMM and RR PCL(plasma cell leukemia, PCL) will be assessed in Phase II study. Phase II clinical study will be conducted after obtaining the RP2D.Determine the specific dosing regimen in Phase II based on the safety, PK and other data from Phase I clinical studies.Phase II clinical study includes 4 cohorts.This trial requires collection of biological samples from all subjects for relevant testing. This clinical trial will enroll 342 patients in Phase I and Phase II studies.
Interventions
DRUGLBL-034 for Injection
Q2W; intravenous infusion
Sponsors
Nanjing Leads Biolabs Co.,Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Agree to follow the trial treatment regimen and visit schedule, voluntarily enroll in the study, and sign the written informed consent form; 2. Age ≥ 18 years at the time of signing the informed consent; 3. Eastern Cooperative Oncology Group (ECOG) Performance Status Scale≤ 1； 4. Documentation of initial diagnosis of multiple myeloma according to IMWG diagnostic criteria,or according to the IMWG 2021 diagnostic criteria, the proportion of circulating plasma cells in peripheral blood is ≥ 5%,have documentation to diagnose PCL； 5. Have a life expectancy of at least 12 weeks； 6. 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
1. 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; 2. 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； 3. Systemic use of corticosteroids or 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); 4. Patients with active hepatitis B or C； 5. Subjects with an active infection that currently requires anti infective therapy; 6. The patient has a Medical history of immunodeficiency, including HIV antibody positive; 7. Women during pregnancy or lactation; 8. The investigator believes that the subject has other conditions that may affect compliance or are not suitable for participating in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 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). | 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(Cohorts 1, 2, and 3) and 2013 IMWG criteria(Cohort 4), 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 . |
| Dose-limiting toxicities（DLT） | The DLT observation period starts from the first dose until 4 weeks after the full dose first administration (including the step-up dosing period, if any). | 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.DLT is defined as toxicity (possible adverse events related to LBL-034) during the DLT observation period . It was used to evaluate the safety of LBL-034 in Phase I study . |
| Maximum tolerated dose (MTD) | The MTD observation period starts from the first dose until 4 weeks after the full dose first administration (including the step-up dosing period, if any). | 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 in Phase I. |
| Occurrence of adverse event (AE) and serious adverse event (SAE) | From all subjects signed the informed consent form up to the completion of the follow-up period of drug withdrawal (90 days after drug withdrawal or before the start of new anti-tumor therapy) | Adverse event (AE) will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0.The safety profile of LBL-034 will be assessed by monitoring the adverse event (AE) and serious adverse event (SAE) in Phase I study. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | 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) | Maximum drug concentration in plasma after administration. |
| Tmax | 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) | After administration,Time to reach maximum drug concentration in plasma. |
| Immunogenicity | 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) | The immunogenicity is evaluated by the incidence of anti-drug antibodies (ADA) and neutralizing antibodies (if applicable) in subjects.Immunogenicity refers to the performance that can elicit an immune response. |
| Minimal Residual Disease (MRD) | 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) | 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. |
| Duration of Response(DOR） | 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) | DOR is defined as the duration from earliest date of disease response (CR、PR 、iCR or iPR) until earliest date of disease progression or death from any cause(if occurring sooner than progression). |
| sBCMA | 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) | serum B-cell maturation antigen(Detect the change of sBCMA in serum) |
Countries
China
Contacts
CONTACTjin lu
PRINCIPAL_INVESTIGATORJin Lu
Peking University People's Hospital
Outcome results
None listed