This single-arm, open-label multicenter Phase I/II study will evaluate the safety, tolerability, anti-tumor activity, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of C-CAR031 in adult participants with GPC3+ advanced/recurrent HCC, who have progressed or are intolerant to at least two prior lines of standardized systemic therapy, and lack of other effective treatments.
Part A (Phase I) is divided into two sections: dose escalation (Part A1) and dose expansion (Part A2). Part A1 will determine the recommended dose for expansion (RDE) to be used in Part A2 (dose expansion) of the study. Part A2 will further evaluate the safety, tolerability and efficacy of C-CAR031 to determine the recommended phase II dose (RP2D) to be used in Part B (Phase II).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
121
Armored and GPC3-targeted autologous CAR T-cells, single infusion intravenously.
ZhongShan Hospital Fudan University
Shanghai, Shanghai Municipality, China
RECRUITINGThe First Affiliated Hospital, Zhejiang University School of Medicine
Hanzhou, Zhejiang, China
RECRUITINGPhase I: Safety and tolerability
• Incidence, correlation and severity of adverse events (AEs).
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Safety and tolerability
• Incidence, correlation and severity of serious adverse events (SAEs)
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Safety and tolerability
• Incidence, correlation and severity of adverse events of special interest (AESIs)
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Safety and tolerability
• Incidence and severity of dose limiting toxicities (DLTs)
Time frame: Throughout the 28 days post C-CAR031 infusion.
Phase I: Safety and tolerability
• Changes from baseline in vital signs (including temperature, systolic and diastolic blood pressure, pulse, respiratory rate, blood oxygen saturation) that are abnormal and of clinically significance.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Safety and tolerability
• Changes from baseline in physical examination (including the general appearance, respiratory, cardiovascular, abdomen, skin, head and neck, lymph nodes, thyroid, musculoskeletal, and neurological systems) that are abnormal and of clinically significance.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Safety and tolerability
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• Changes from baseline in Eastern Cooperative Oncology Group (ECOG) score that are abnormal and of clinically significance (ECOG performance status score above 1).
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Safety and tolerability
• Changes from baseline in 12-lead electrocardiograms (ECGs) that are abnormal and of clinically significance.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Safety and tolerability
• Changes from baseline in laboratory test results (including the clinical chemistry, haematology, coagulation, urinalysis, serology, pregnancy assessments) that are abnormal and of clinically significance.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• Objective response rate (ORR) assessed by independent review committee (IRC) and evaluated according to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Pharmacokinetics
• Quantification of CAR transgene DNA copies of C-CAR031 in peripheral blood.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Pharmacokinetics
• Time to reach maximum concentration (Tmax) of C-CAR031 in peripheral blood
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Pharmacokinetics
• Maximum observed concentration (Cmax) of C-CAR031 in peripheral blood
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Pharmacokinetics
• Area under the curve 28 days after C-CAR031 infusion(AUC0-28d)
Time frame: Throughout the 28 days post C-CAR031 infusion.
Phase I: Pharmacokinetics
• Last measurable concentration (Clast)
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Pharmacokinetics
• Time of Clast (Tlast)
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Pharmacokinetics
• Area under the curve from time 0 to the time of the last quantifiable concentration (AUClast)
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Anti-tumor activity
• ORR assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Anti-tumor activity
• Disease control rate (DCR) assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Anti-tumor activity
• Duration of response (DoR) assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Anti-tumor activity
• Durable response rate (DRR) assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Anti-tumor activity
• Time to response (TTR) assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Anti-tumor activity
• Progression-free survival (PFS) assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Anti-tumor activity
• Change in tumor size assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase I: Anti-tumor activity
• Overall survival (OS)
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• OS
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• ORR assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• DCR assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• DoR assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• DRR assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• TTR assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• PFS assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• Change in tumor size assessed by the Investigator and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• DCR assessed by the IRC and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• DoR assessed by the IRC and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• DRR assessed by the IRC and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• TTR assessed by the IRC and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• PFS assessed by the IRC and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Anti-tumor activity
• Change in tumor size assessed by the IRC and evaluated according to RECIST 1.1 criteria
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Safety and tolerability
• Incidence, correlation and severity of AEs.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Safety and tolerability
Incidence, correlation and severity of SAEs.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Safety and tolerability
• Incidence, correlation and severity of AESIs.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Safety and tolerability
• Changes from baseline in vital signs (including temperature, systolic and diastolic blood pressure, pulse, respiratory rate, blood oxygen saturation) that are abnormal and of clinically significance.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Safety and tolerability
• Changes from baseline in physical examination (including the general appearance, respiratory, cardiovascular, abdomen, skin, head and neck, lymph nodes, thyroid, musculoskeletal, and neurological systems) that are abnormal and of clinically significance.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Safety and tolerability
• Changes from baseline in Eastern Cooperative Oncology Group (ECOG) score that are abnormal and of clinically significance (ECOG performance status score above 1).
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Safety and tolerability
• Changes from baseline in 12-lead electrocardiograms (ECGs) that are abnormal and of clinically significance.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Safety and tolerability
• Changes from baseline in laboratory test results that are abnormal and of clinically significance.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Pharmacokinetics
• Quantification of CAR transgene DNA copies of C-CAR031 in peripheral blood.
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Pharmacokinetics
• Tmax of C-CAR031 in peripheral blood
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Pharmacokinetics
• Cmax of C-CAR031 in peripheral blood
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Pharmacokinetics
• AUC0-28d of C-CAR031 in peripheral blood
Time frame: Throughout the 28 days post C-CAR031 infusion.
Phase II: Pharmacokinetics
• Tlast of C-CAR031 in peripheral blood
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Pharmacokinetics
• Clast of C-CAR031 in peripheral blood
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.
Phase II: Pharmacokinetics
• AUClast of C-CAR031 in peripheral blood
Time frame: Throughout the study period, which extends up to 24 months after the administration of C-CAR031.