This study is an open-label, multicenter, dose-escalation and cohort expansion phase I clinical study to evaluate the safety, tolerability, pharmacokinetics characteristics or preliminary efficacy and antitumor activity in patients with Locally advanced or metastatic non-small cell lung cancer and other solid tumors.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Administration by intravenous infusion for a cycle of 3 weeks.
Shanghai East Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGPhase Ia: 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 Ia: 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 Ia: 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-077 . The type, frequency and severity of TEAE will be evaluated during the treatment of GNC-077.
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-077.
Time frame: Up to approximately 24 months
Cmax
Maximum serum concentration (Cmax) of GNC-077 will be investigated.
Time frame: Up to approximately 24 months
Tmax
Time to maximum serum concentration (Tmax) of GNC-077 will be investigated.
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Time frame: Up to approximately 24 months
AUC0-inf
AUC0-inf is defined as area under the concentration-time curve from 0 to inf.
Time frame: Up to approximately 24 months
AUC0-t
AUC0-t is defined as area under the serum concentration-time curve from time 0 to the time of the last measurable concentration.
Time frame: Up to approximately 24 months
CL (Clearance)
CL in the serum of GNC-077 per unit of time will be investigated.
Time frame: Up to approximately 24 months
T1/2
Half-life (T1/2) of GNC-077 will be investigated.
Time frame: Up to approximately 24 months
ADA (anti-drug antibody)
Frequency of anti-GNC-077 antibody (ADA) will be investigated.
Time frame: Up to approximately 24 months
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
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
Progression-free survival (PFS)
The PFS is defined as the time from the participant's first dose of GNC-077 to the first date of either disease progression or death, whichever occurs first.
Time frame: Up to approximately 24 months
Overall survival (OS)
Overall survival (OS) is defined as the time between the subject's randomization date and subject's death.
Time frame: Up to approximately 24 months