In this study, the safety and preliminary efficacy of GNC-038 in participants with recurrent or refractory Diffuse Large B-cell lymphoma (DLBCL) will be investigated to assess the dose-limiting toxicity (DLT), maximum tolerated dose (MTD) or maximum administered dose (MAD) for MTD is not reached of GNC-038. The recommended dose for phase II (RP2D) clinical study will also be determined.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Administration by intravenous infusion
Shenzhen Second People's Hospital
Shenzhen, Guangdong, China
Affiliated Hospital of Hebei University
Baoding, Hebei, China
The First Affiliated Hospital of Henan University of Science and Technology
Luoyang, Henan, China
Ruijin Hospital, Shanghai JiaoTong University School of Medicine
Shanghai, Shanghai Municipality, China
Dose limiting toxicity (DLT)
The incidence and severity of adverse events during treatment were graded according to the National Cancer Institute Standard for Common Terminology for Adverse Events (NCI-CTCAE, v5.0).
Time frame: Up to 21 days after the first dose of GNC-038
Maximum tolerated dose (MTD) or maximum administrated dose (MAD)
In the dose increment stage, the highest dose whose estimated DLT rate is closest to the target DLT rate but does not exceed the upper bound of the equivalent interval of DLT rate is selected as MTD.
Time frame: Up to 21 days after the first dose of GNC-038
Treatment-Emergent Adverse Event (TEAE)
TEAE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally emerging, or any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition during the treatment of GNC-038. The type, frequency and severity of TEAE will be evaluated during the treatment of GNC-038.
Time frame: Up to approximately 24 months
The recommended dose for phase II clinical study(RP2D)
The RP2D is defined as the dose level chosen by the sponsor (in consultation with the investigators) for phase II study, based on safety, tolerability, efficacy, PK, and PD data collected during the dose escalation study of GNC-038.
Time frame: Up to 21 days after the first dose of GNC-038
ORR (Objective Response Rate )
ORR is defined as the percentage of participants, who has a CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions). The percentage of participants who experiences a confirmed CR or PR is according to RECIST 1.1.
Time frame: Up to approximately 24 months
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PFS (Progression-free Survival)
The PFS is defined as the time from the participant's first dose of GNC-038 to the first date of either disease progression or death, whichever occurs first.
Time frame: Up to approximately 24 months
DCR (Disease Control Rate)
The DCR is defined as the percentage of participants who has a CR, PR, or Stable Disease (SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease \[PD: at least a 20% increase in the sum of diameters of target lesions and an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD\]).
Time frame: Up to approximately 24 months
DOR (Duration of Response)
The DOR for a responder is defined as the time from the participant's initial objective response to the first date of either disease progression or death, whichever occurs first.
Time frame: Up to approximately 24 months
CR (Complete Response)
Disappearance of all target lesions.
Time frame: Up to approximately 24 months
Adverse Events of special interest (AESI)
AESI is an event of scientific and medical interest specific to the sponsor's product or research project.
Time frame: Up to approximately 24 months
Peak Plasma Concentration(Cmax)
Maximum serum concentration (Cmax) of GNC-038 will be investigated.
Time frame: Up to 21 days after the first dose of GNC-038
Incidence and titer of ADA (Anti-drug antibody)
Frequency and titer of anti-GNC-038 antibody (ADA) will be evaluated.
Time frame: Up to approximately 24 months
Incidence and titer of Nab
Incidence and titer of Nab of GNC-038 will be evaluated.
Time frame: Up to approximately 24 months
Trough steady-state concentration(Css)
Concentration of GNC-038 at steady state plateau will be investigated.
Time frame: Up to 14 days after the first dose of GNC-038
Time to reach maximum concentration (Tmax)
Time to maximum serum concentration (Tmax) of GNC-038 will be investigated.
Time frame: Up to 21 days after the first dose of GNC-038
AUC0-inf
Area under the plasma concentration-time curve from time 0 extrapolated to infinite (AUC0-inf).
Time frame: Up to 21 days after the first dose of GNC-038
AUC0-t
Area under the plasma concentration-time curve from time 0 to last time of quantifiable concentration (AUC0-t).
Time frame: Up to 21 days after the first dose of GNC-038
Plasma clearance (CL)
To study the serum clearance rate of GNC-038 per unit time.
Time frame: Up to 21 days after the first dose of GNC-038
Elimination half life (T1/2)
Half-life (T1/2) of GNC-038 will be investigated.
Time frame: Up to 21 days after the first dose of GNC-038