In this study, the safety and preliminary efficacy of GNC-038 in patients with r relapsed or refractory primary central nervous system lymphoma (PCNSL) and relapsed or refractory secondary central nervous system lymphoma (SCNSL) 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
7
Administration by intravenous infusion
Beijing Tiantan Hospital, Capital Medical University
Beijing, Beijing Municipality, China
Beijing GoBroad Boren Hospital
Beijing, Beijing Municipality, China
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 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 17 days after the first dose
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 17 days after the first dose
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 36 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 17 days after the first dose
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 36 months
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 36 months
DCR (Disease Control Rate)
Number of patients showing Complete Response (CR, disappearance of all target lesions) or Partial Response (PR, at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) based on RECIST Criteria Version 1.0 (assessed by CT and/or MRI) for the best response.
Time frame: Up to approximately 36 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 36 months
CR (Complete Response)
Disappearance of all target lesions.
Time frame: Up to approximately 36 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 36 months
Peak Plasma Concentration(Cmax)
Maximum serum concentration (Cmax) of GNC-038 will be investigated.
Time frame: Up to 17 days after the first dose
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 36 months
Incidence and titer of Nab
Incidence and titer of Nab of GNC-038 will be evaluated.
Time frame: Up to approximately 36months
Time to reach maximum concentration (Tmax)
Time to maximum serum concentration (Tmax) of GNC-038 will be investigated.
Time frame: Up to 17 days after the first dose
AUC0-inf
Area under the plasma concentration-time curve from time 0 extrapolated to infinite (AUC0-inf).
Time frame: Up to 17 days after the first dose
AUC0-t
Area under the plasma concentration-time curve from time 0 to last time of quantifiable concentration (AUC0-t).
Time frame: Up to 14 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 17 days after the first dose
Elimination half life (T1/2)
Blood concentration - Area under time line.
Time frame: Up to 17 days after the first dose
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