An open, multicenter, Phase I clinical study to evaluate the safety, tolerability, pharmacokinetics/pharmacokinetics, and antitumor activity of GNC-038 quad-specific antibody injection in relapsed or refractory non-Hodgkin's lymphoma, relapsed or refractory acute lymphoblastic leukemia, and refractory or metastatic solid tumors.
Phase Ia: To observe the safety and tolerability of GNC-038 in patients with relapsed or refractory non-Hodgkin lymphoma (R/R NHL)/relapsed or refractory acute lymphoblastic leukemia (R/R ALL), To determine the maximum tolerated dose (MTD) or maximum administration dose (MAD) and dose-limiting toxicity (DLT) of GNC-038 without MTD and recommend the dose for subsequent clinical studies. Phase Ib: To further observe the safety and tolerability of GNC-038 at the Phase Ia recommended dose to determine the Phase II recommended dose (RP2D).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
47
Administration by intravenous infusion.
The Second Hospital of Anhui Medical University
Hefei, Anhui, China
Peking University Third Hospital
Beijing, Beijing Municipality, China
Chongqing University Cancer Hospital
Chongqing, Chongqing Municipality, China
Dose limiting 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 14 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 14 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 24 months
The recommended dose for future clinical study
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 14 days after the first dose of GNC-038
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
Cmax: Maximum serum concentration of GNC-038
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The First Affiliated Hospital of Chongqing Medical University
Chongqing, Chongqing Municipality, China
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, China
Nanfang Hospital of Southern Medical University
Guangzhou, Guangdong, China
Xiangya Hospital Central South University
Changsha, Hunan, China
Shanghai Tongji Hospital
Shanghai, Shanghai Municipality, China
Hematology Hospital, Chinese Academy of Medical Sciences
Tianjin, Tianjin Municipality, China
The Second Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, Zhejiang, China
Maximum serum concentration (Cmax) of GNC-038 will be investigated.
Time frame: Up to 14 days after the first dose of GNC-038
Css: Concentration of GNC-038 at steady state plateau
Concentration of GNC-038 at steady state plateau will be investigated.
Time frame: Up to 14 days after the first dose of GNC-038
Tmax: Time to maximum serum concentration (Tmax) of GNC-038
Time to maximum serum concentration (Tmax) of GNC-038 will be investigated.
Time frame: Up to 14 days after the first dose of GNC-038
T1/2: Half-life of GNC-038
Half-life (T1/2) of GNC-038 will be investigated.
Time frame: Up to 14 days after the first dose of GNC-038
AUC0-inf: Area under the serum concentration-time curve from time 0 to infinity
Blood concentration - Area under time line.
Time frame: Up to 14 days after the first dose of GNC-038
AUC0-t: Area under the serum concentration-time curve from time 0 to the time of the last measurable concentration
Blood concentration - Area under time line.
Time frame: Up to 14 days after the first dose of GNC-038
CL: Clearance in the serum of GNC-038 per unit of time
To study the serum clearance rate of GNC-038 per unit time.
Time frame: Up to 14 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 (Neutralizing antibody)
Incidence and titer of Nab of GNC-038 will be evaluated.
Time frame: Up to approximately 24 months
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
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
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
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