A Pharmacokinetic Study of Zolbetuximab (IMAB362) in Chinese Subjects with Locally Advanced Unresectable or Metastatic Gastric or Gastro-esophageal Junction (GEJ) Adenocarcinoma
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Zolbetuximab will be administered as a 2-hour intravenous infusion
Site CN86001
Guangzhou, China
Pharmacokinetics (PK) of zolbetuximab: Area under the concentration-time curve (AUC) from the time of dosing extrapolated to time infinity (AUCinf)
AUCinf will be recorded from the PK serum samples collected.
Time frame: Up to 15 months
PK of zolbetuximab: Percentage of AUCinf (AUCinf (%extrap))
AUCinf (%extrap) will be recorded from the PK serum samples collected.
Time frame: Up to 15 months
PK of zolbetuximab: AUC from the time of dosing to the last measurable concentration (AUClast)
AUClast will be recorded from the PK serum samples collected.
Time frame: Up to 15 months
PK of zolbetuximab: AUC from the time of dosing to the start of the next dosing interval (AUCtau)
AUCtau will be recorded d from the PK serum samples collected.
Time frame: Up to 15 months
PK of zolbetuximab: Maximum concertation (Cmax)
Cmax will be recorded from the PK serum samples collected.
Time frame: Up to 15 months
PK of zolbetuximab: Concentration immediately prior to dosing at multiple dosing (Ctrough)
Ctrough will be recorded from the PK serum samples collected.
Time frame: Up to 15 months
PK of zolbetuximab: Time of the maximum concentration (tmax)
tmax will be recorded from the PK serum samples collected.
Time frame: Up to 15 months
PK of zolbetuximab: Terminal elimination half-life (t1/2)
t1/2 will be recorded from the PK serum samples collected.
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Time frame: Up to 15 months
PK of zolbetuximab: Time of the last measurable concentration (tlast)
tlast will be recorded from the PK serum samples collected.
Time frame: Up to 15 months
PK of zolbetuximab: Clearance (CL)
CL will be recorded from the PK serum samples collected.
Time frame: Up to 15 months
PK of zolbetuximab: Apparent volume of distribution during the terminal phase (Vz)
Vz will be recorded from the PK serum samples collected.
Time frame: Up to 15 months
PK of zolbetuximab: Accumulation ratio calculated using AUC (Rac(AUC))
Rac(AUC) will be recorded from the PK serum samples collected.
Time frame: Up to 15 months
PK of zolbetuximab: Rac (Cmax)
Rac(Cmax)will be recorded from the PK serum samples collected.
Time frame: Up to 15 months
Number of participants with adverse events (AEs)
An AE is any untoward medical occurrence in a subject administered a study drug, and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product whether or not considered related to the medicinal product. AE is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event. Treatment Emergent Adverse Event (TEAE) is defined as an adverse event observed after starting administration of the study drug and within 30 days after the last dose of study drug.
Time frame: Up to 15 months
Number of participants with laboratory test abnormalities and/or AEs
Number of participants with potentially clinically significant laboratory values.
Time frame: Up to 13 months
Number of participants with body weight abnormalities and/or AEs
Number of participants with potentially clinically significant body weight changes.
Time frame: Up to 13 months
Number of participants with vital sign abnormalities and/or AEs
Number of participants with potentially clinically significant vital sign values.
Time frame: Up to 13 months
Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs
Number of participants with potentially clinically significant 12-ECG values.
Time frame: Up to 13 months
Eastern Cooperative Oncology Group (ECOG) performance status score
ECOG performance status will be assessed on the following 6-point scale; 0=Fully active, able to carry on all pre-disease performance without restriction; 1=Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature, (e.g., light housework, office work); 2=Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5=Dead. Decrease in the score indicates an improvement. Increase in the score indicates a decline in performance.
Time frame: Up to 13 months
Proportion of anti-drug antibody (ADA) positive participants
Proportion of participants with presence of ADA will be assessed.
Time frame: Up to 15 months
Objective Response Rate (ORR)
ORR is defined as the proportion of subjects whose best overall response (BOR) is rated as compete response (CR) or partial response (PR) among all analyzed subjects. Complete response (CR) of target lesions is defined as disappearance of all target lesions. Any pathological lymph nodes, if chosen as target lesions, must have a reduction in the short axis to \< 10 mm from the baseline measurement. Partial response (PR) of target lesions is defined as at least a 30% decrease in the sum of diameters of target lesions (long diameter for non-pathological lymph nodes and short diameter for pathological lymph nodes), taking the baseline sum diameter as a reference. BOR rated as CR or PR should be confirmed by at least 2 consecutive assessments performed at a minimum interval of 4 weeks. Subjects must therefore meet the criteria for CR or PR continuously for 4 weeks or longer.
Time frame: Up to 12 months
Duration of Progression Free Survival (PFS)
PFS is defined as the time from the start of study treatment until death from any cause, or radiographic or clinical disease progression per RECIST 1.1, whichever occurs earlier.
Time frame: Up to 12 months
Disease Control Rate (DCR)
DCR is defined as the proportion of subjects whose BOR is rated as CR, PR, or stable disease (SD) among all analyzed subjects. SD of target lesions is defined as neither sufficient shrinkage to qualify for PR, nor sufficient increase to qualify for progressive disease (PD), taking the smallest sum diameter on study as a reference. (PD) of the target lesions is defined as at least a 20% increase in the sum of the diameters of target lesions (long diameter for non-pathological lymph nodes and short diameter for pathological lymph nodes), taking the smallest sum on study (this includes the baseline sum if that is the smallest on study) as a reference. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
Time frame: Up to 12 months
Duration of Response (DOR)
DOR is defined as the time from the date of the first response (CR or PR) per RECIST 1.1 to the date of radiological PD, clinical progression only if radiological assessment is not available, or death, whichever occurs earlier.
Time frame: Up to 12 months
Duration of Overall Survival (OS)
OS is defined as the time from the date of randomization until the date of death from any cause.
Time frame: Up to 15 months