To explore the safety and efficacy of GNC-038 in relapsed or refractory NK/T cell lymphoma, vascular immunomother T cell lymphoma, and other relapsed or refractory NHL, and to determine MTD, MAD, DLT, and RP2D of GNC-038, as well as its pharmacokinetic characteristics and immunogenicity.
Phase Ib: To explore the safety and preliminary effectiveness of GNC-038 under the administration mode of "intravenous infusion for 2h to 4h, once a week (IV, QW), 2 weeks as one cycle", and to determine MTD, MAD, DLT and RP2D of GNC-038. The pharmacokinetic characteristics and immunogenicity of GNC-038 will be evaluated. Phase II: To explore the efficacy, safety and tolerability, pharmacokinetic characteristics and immunogenicity of GNC-038.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
4
Administration by intravenous infusion
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, China
Phase Ib: Dose Limited Toxicity (DLT)
The incidence and severity of adverse events (TEAE) 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 16 days after the first dose
Phase Ib: Maximum Tolerated dose (MTD) or maximum administered 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 16 days after the first dose
Phase Ib: 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
Phase Ib: Recommended Phase II Dose (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 16 days after the first dose
Phase II: Objective response rate (ORR)
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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Phase Ib: Objective response rate (ORR)
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
Phase Ib: Progression-free survival (PFS)
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
Phase Ib: Disease control rate (DCR)
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
Phase Ib:Duration of response (DOR)
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
Phase Ib: Complete Response (CR)
Disappearance of all target lesions.
Time frame: Up to approximately 24 months
Phase Ib: 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
Phase Ib: Cmax
Maximum serum concentration (Cmax) of GNC-038 will be investigated.
Time frame: Up to 16 days after the first dose
Phase Ib:Tmax
Time to maximum serum concentration (Tmax) of GNC-038 will be investigated.
Time frame: Up to 16 days after the first dose
Phase Ib:AUC0-inf
Blood concentration - Area under time line.
Time frame: Up to 16 days after the first dose
Phase Ib: AUC0-T
Blood concentration - Area under time line.
Time frame: Up to 16 days after the first dose
Phase Ib: CL(Clearance)
To study the serum clearance rate of GNC-038 per unit time.
Time frame: Up to 16 days after the first dose
Phase Ib: T1/2
Half-life (T1/2) of GNC-038 will be investigated.
Time frame: Up to 16 days after the first dose
Phase Ib: Anti-drug antibody (ADA)
Frequency and titer of anti-GNC-038 antibody (ADA) will be evaluated.
Time frame: Up to approximately 24 months
Phase II: Progression-free survival (PFS)
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
Phase II: Disease control rate (DCR)
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
Phase II:Duration of response (DOR)
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
Phase II: 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