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
Overview
- Phase
- Phase 1
- Intervention
- LBL-034 for Injection
- Conditions
- Relapsed/Refractory Multiple Myeloma
- Sponsor
- Nanjing Leads Biolabs Co.,Ltd
- Enrollment
- 342
- Locations
- 26
- Primary Endpoint
- Objective Response Rate (ORR)
- Status
- Recruiting
- Last Updated
- 4 months ago
Overview
Brief Summary
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 Relapsed/Refractory Multiple Myeloma (R/R MM).
Detailed Description
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 IIa 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 the treatment of R/R MM and R/R leukaemia plasmacytic (plasma cell leukemia, PCL) will be evaluated in Phase IIa study.Phase IIa clinical study will be conducted after obtaining the RP2D.Determine the specific dosing regimen in Phase IIa based on the safety, PK and other data from Phase I clinical studies.Phase IIa 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 IIa studies.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Agree to follow the trial treatment regimen and visit schedule, voluntarily enroll in the study, and sign the written informed consent form;
- •Age ≥ 18 years at the time of signing the informed consent;
- •Eastern Cooperative Oncology Group (ECOG) Performance Status Scale≤ 1；
- •Documentation of 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 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);
- •Patients with active hepatitis B or C；
- •Subjects with an active infection that currently requires intravenous anti infective therapy;
- •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.
Arms & Interventions
LBL-034
LBL-034 for Injection; Initial dose - MTD; Q2W
Intervention: LBL-034 for Injection
Outcomes
Primary Outcomes
Objective Response Rate (ORR)
Time Frame: 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 IIa study .
Dose-limiting toxicities（DLT）
Time Frame: 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)
Time Frame: 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.
Secondary Outcomes
- 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))
- 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))
- 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))
- 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))
- 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))
- 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))