Phase I main objectives: To observe the safety and preliminary efficacy of GNC-035 in patients with relapsed/refractory non-Hodgkin lymphoma and other hematological malignancies, to determine the DLT and MTD, or MAD, and to determine RP2D. Phase II Main objective: To explore the efficacy of GNC-035 in patients with relapsed/refractory non-Hodgkin lymphoma and other hematological malignancies.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
GNC-035 was administered by intravenous infusion for 2 h-4 h, once a week ( IV, QW ), 3 weeks as a cycle.
Beijing Cancer Hospital
Beijing, Beijing Municipality, China
RECRUITINGPhase I: Dose limiting toxicity (DLT)
DLTs are assessed according to NCI-CTCAE v5.0 during the first cycle and defined as occurrence of any of the toxicities in DLT definition if judged by the investigator to be possibly, probably or definitely related to study drug administration.
Time frame: Up to 21 days after the first dose
Phase I: Maximum tolerated dose (MTD)
MTD is defined as the highest dose level at which no more than 1 in 6 participants experienced a DLT during the first cycle .
Time frame: Up to 21 days after the first dose
Phase I: 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-035. The type, frequency and severity of TEAE will be evaluated during the treatment of GNC-035.
Time frame: Up to approximately 24 months
Phase I: 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-035.
Time frame: Up to 21 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 I: 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
Progression-free survival (PFS)
The PFS is defined as the time from the participant's first dose of GNC-035 to the first date of either disease progression or death, whichever occurs first.
Time frame: Up to approximately 24 months
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
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 I: Complete Response (CR)
Complete response (CR) is defined as all tumor target lesions disappeared, no new lesions appeared, and tumor markers were normal for at least 4 weeks.
Time frame: Up to approximately 24 months
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-035. The type, frequency and severity of TEAE will be evaluated during the treatment of GNC-035.
Time frame: Up to approximately 24 months
Phase I: Cmax
Maximum Drug Concentration (Cmax) of GNC-035 will be investigated.
Time frame: Up to 21 days after the first dose
Phase I: Tmax
Time at Which the Maximum (Tmax) of GNC-035 will be investigated.
Time frame: Up to 21 days after the first dose
Phase I: AUC0-inf
Area Under the Curve(0-inf)of GNC-035 will be investigated.
Time frame: Up to 21 days after the first dose
Phase I: AUC0-T
Area Under the Curve(0-t)of GNC-035 will be investigated.
Time frame: Up to 21 days after the first dose
Phase I: CL
Rate of clearance of GNC-035 will be investigated.
Time frame: Up to 21 days after the first dose
Phase Ib: T1/2
Half-life (T1/2) of GNC-035 will be investigated.
Time frame: Up to 21 days after the first dose
Phase I: Anti-drug antibody (ADA)
Frequency of anti-GNC-035 antibody (ADA) will be investigated.
Time frame: Up to approximately 24 months