This is a First-in-Human, open-label, early dose-escalation clinical study to evaluate the safety and preliminary efficacy of GC511B CAR T cell injection in Adult with DLL3+ r/r SCLC trial participants.
This is a First-in-Human, open-label, early dose-escalation clinical study to evaluate the safety and preliminary efficacy of GC511B CAR T cell injection in Adult with DLL3+ r/r SCLC trial participants. this study consists of two parts: dose escalation and dose expansion: Dose Escalation: This part consists of two stages:Stage 1: Accelerated titration design to explore the effective starting dose;Stage 2: Bayesian optimal interval (BOIN) design to explore the MAD/MTD.The BOIN design will start with aDL1 as determined in Stage 1 and continue until either 9 trial participants have been enrolled at a single dose level (DL) or the total number of trial participants reaches 11.Starting with BOIN stage DL3, the first and second trial participants were reinfused at least 2 weeks apart.During the dose-escalation phase, following each dose level (DL) and/or scheduled infusion time point, the Safety Review Committee (SRC) will evaluate all adverse events (AEs), serious adverse events (SAEs), laboratory safety data from subjects in the DLT observation period, as well as all other relevant available data, to determine the next DL to be explored and/or dosing schedule and to provide recommendations for subsequent study conduct. Dose expansion : The dose expansion phase will be initiated at the defined RDE to further investigate the safety, feasibility, CK, immunogenicity, PD, and preliminary antitumor activity of GC511B monotherapy and/or combination therapy. Up to 4 expansion cohorts may be opened to evaluate specific DLs and indications with up to 20 response-evaluable trial participants included in each cohort.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
55
This product is a lentiviral gene-modified autologous chimeric antigen receptor T-cell product that GC511B.Administration of GC511B CAR T-Cells a dose levels of DL1,DL2,DL3 and DL4 are administrated for each trial participants.Single IV infusion.
Cancer Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
RECRUITINGBeijing Gobroad Hospital
Beijing, Beijing Municipality, China
RECRUITINGDose-Limiting Toxicity (DLT) Rate
DLT is defined as an AE that occurs within 28 days of GC511B CAR-T product reinfusion.DLT will be evaluated according to NCI-CTCAE V5.0 criteria
Time frame: 28 days
Adverse Events (AEs)
Proportion of trial participants experiencing AE within 15 years after infusion of GC511B CAR-T cell injection.
Time frame: Up to 15 years from treatment discontinuation
Changes in vital signs to baseline
Include body temperature by CTCAE V5.0
Time frame: Up to 24 months from treatment discontinuation
Changes in Electrocardiogram(ECG) to baseline
ECG QT intervals
Time frame: Up to 24 months from treatment discontinuation
Changes in vital signs to baseline
Systolic and diastolic blood pressure by CTCAE V5.0
Time frame: Up to 24 months from treatment discontinuation
Changes in vital signs to baseline
Respiratory rate by CTCAE V5.0
Time frame: Up to 24 months from treatment discontinuation
Changes in vital signs to baseline
Pulse by CTCAE V5.0
Time frame: Up to 24 months from treatment discontinuation
Area under the concentration time curve (AUC)
Cytokinetics (CK) profile of GC511B CAR-T celltherapy
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Time frame: Up to 15 years from treatment discontinuation
Maximum plasma concentration (Cmax)
Cytokinetics (CK) profile of GC511B CAR-T celltherapy
Time frame: Up to 15 years from treatment discontinuation
Time to maximum plasma concentration (Tmax)
Cytokinetics (CK) profile of GC511B CAR-T celltherapy
Time frame: Up to 15 years from treatment discontinuation
Last detectable time point(Tlast)
Cytokinetics (CK) profile of GC511B CAR-T celltherapy
Time frame: Up to 15 years from treatment discontinuation
Last quantifiable concentratione (Clast)
Cytokinetics (CK) profile of GC511B CAR-T celltherapy
Time frame: Up to 15 years from treatment discontinuation
Replication-competent lentivirus(RCL) in peripheral blood
RCL is monitored through mandatory viral testing
Time frame: At baseline and within the selected time after the infusion of GC511B CAR-T cell
Objective Response Rate (ORR)
ORR is defined as the percentage of subjects with confirmed CR or PR, and the denominator is defined as the number of subjects in the response evaluable set
Time frame: Up to 15 years study discontinuation
Best Overall Response (BOR)
BOR is defined as the best response a subject achieves based on evaluable data collected at all available time points prior to progression, or the last evaluable assessment result in the absence of disease progression or the initiation of subsequent anti-tumor therapy.
Time frame: Up to 15 years study discontinuation
Duration of Response (DoR)
DoR is defined as the time from the date of the first documented objective response (subsequently confirmed) to the first documented disease progression or death (for any reason in the absence of disease progression).
Time frame: Up to 15 years study discontinuation
Disease Control Rate(DCR)
DCR is defined as the percentage of trial participants who achieve and maintain a CR or PR after receiving CAR-T therapy, or who achieve SD and maintain that response.for at least 7 weeks
Time frame: 7Weeks
Time to First Response(TTR)
TTR is defined as the time from the date of CAR-T product reinfusion to the date of the first documented confirmed objective response that is subsequently confirmed
Time frame: Up to 15 years study discontinuation
Percentage Change in Tumor Size
Depth of tumor response is defined as the maximum percentage of shrinkage of TL compared with baseline.
Time frame: Up to 15 years study discontinuation
Progression-free Survival(PFS)
PFS is defined as the time from the date of CAR-T product reinfusion to the date of objective disease progression or death (all-cause death in the absence of progression).
Time frame: Up to 15 years study discontinuation
Overall Survival(OS)
OS is defined as the time from the date of CAR-T product reinfusion to the date of all-cause death, regardless of whether the subject receives another anti-tumor therapy.
Time frame: Up to 15 years study discontinuation