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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
342
Q2W; intravenous infusion
The First Affiliated Hospital of Wannan Medical College
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(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 .
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).
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.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 .
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).
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 in Phase I.
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).
Occurrence of adverse event (AE) and serious adverse event (SAE)
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.
Time frame: 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)
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Wuhu, Anhui, China
Peking University People's Hospital
Beijing, Beijing Municipality, China
RECRUITINGThe First Affiliated Hospital of Xiamen University
Xiamen, Fujian, China
RECRUITINGSun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
RECRUITINGShenzhen Second People's Hospital
Shenzhen, Guangdong, China
RECRUITINGThe Afliliated Hospital of Guizhou Medical Univeristy
Guiyang, Guizhou, China
RECRUITINGThe Second Affiliated Hospital of Hainan Medical University
Haikou, Hainan, China
RECRUITINGThe First Affiliated Hospital of Henan University
Luoyang, Henan, China
RECRUITINGHenan Cancer Hospital
Zhengzhou, Henan, China
RECRUITINGThe First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, China
RECRUITING...and 11 more locations
Cmax
Maximum drug concentration in plasma after administration.
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)
Tmax
After administration,Time to reach maximum drug concentration in plasma.
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)
Immunogenicity
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.
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)
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.
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)
Duration of Response(DOR)
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).
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)
sBCMA
serum B-cell maturation antigen(Detect the change of sBCMA in serum)
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)