CT011 Autologous CAR-T Cells in Patients With Hepatocellular Carcinoma at Risk of Recurrence After Surgical Resection

NCT06560827 | Recruiting Phase 1

• 1 other identifier: CT011-HCC-03
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 15

Brief Summary

A Single-arm, Open-label, Multicenter, Phase Ib Clinical Trial to Evaluate the Safety and Efficacy of CT011 Autologous CAR-T Cells in Patients with Hepatocellular Carcinoma at Risk of Recurrence after Surgical Resection.

Conditions

HCC

Keywords

IIIa; GPC3; HCC; CT011

Outcome Measures

Primary Outcomes (3)

• Incidence and severity of treatment-emergent adverse events (TEAE)

  According to the two-level classification of System Organ Classification (SOC) and Preferred Term, calculate the number and incidence of each type of AE separately; List and describe the severity of AE and its relationship with experimental treatment.

  Up to 12 months

• Incidence and severity of treatment-related adverse events (TRAE)

  List the AE related to the experimental treatment separately, and calculate the number and incidence of adverse events (TRAEs) related to the experimental treatment.

  Up to 12 months

• Incidence and severity of adverse events of special interest (AESI)

  Regardless of the causal relationship, the following events occurring after CAR-T cell infusion until 12 months after the last infusion are considered AESI: any ≥ grade 3 CRS; ≥ Level 3 HLH; Any ICANS level ≥ 3; Any grade ≥ 2 infusion related reaction (IRR); Any grade 3 or higher allergic reactions, etc. Evaluate the incidence and rate of AESI.

  Up to 12 months

Secondary Outcomes (14)

• Recurrence free survival (RFS)

  Up to 12 months

• W24, W48, and W72 RFS rates

  Up to 12 months

• Time to recurrence (TTR)

  Up to 12 months

• Time to intrahepatic recurrence (TT-IHR)

  Up to 12 months

• Time to extrahepatic spread (TT-EHS)

  Up to 12 months

Study Arms (1)

CT011 CAR-GPC3 T Cells Injection

EXPERIMENTAL

This trial is a single-arm, open-label, exploratory trial, and no statistical hypothesis is made for sample size estimation. It is planned to enroll approximately 30 participants to receive CT011 infusion.

Biological: CT011 CAR-GPC3 T Cells Injection

Interventions

CT011 CAR-GPC3 T Cells Injection BIOLOGICAL

The dose selection for this trial was mainly based on the preliminary safety and efficacy results of CT011-HCC-01 trial in subjects with advanced HCC, in which 3 and 5 subjects in the 2.5 × 108 cell and 5.0 × 108 cell dose groups, respectively, completed a single infusion of CT011. The results showed that the two dose groups of CT011 were generally well tolerated in HCC subjects who failed to standard treatment, with controllable safety, and showed preliminary anti-tumor efficacy.

CT011 CAR-GPC3 T Cells Injection

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• To be included in the trial, participants must meet all of the following criteria:
• Volunteer to participate in the clinical trial; fully understand and are informed of this trial and sign the informed consent form; Willing to follow and able to complete all trial procedures;
• Age 18-75 years, inclusive, male or female;
• Initially diagnosed with CNLC stage IIIa HCC with any of the following vascular tumor thrombi and absence of atrial tumor thrombi on preoperative imaging:
• Portal vein tumor thrombus (PVTT);
• Hepatic vein tumor thrombus (HVTT);
• Inferior vena cava tumor thrombus (IVCTT);
• Has undergone surgical resection:
• Pathological evaluation of surgical resection specimen with negative margins;
• Preoperative conversion/neoadjuvant therapy and/or postoperative therapy are allowed;
• The participant has recovered from liver resection and postoperative progressive increase in AFP level(including: a. AFP increase of at least 20% in any 3 months after surgery; or b. AFP increase of ≥ 10% in any 2 consecutive tests after surgery) with a potential tendency to recurrence as assessed by the investigator.
• Tumor tissue samples positive for GPC3 by immunohistochemistry (IHC) (staining intensity ≥ 1 +, percentage of stained tumor cells ≥ 10%);
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (within 7 days prior to apheresis);
• Child-Pugh score ≤ 7 points (within 7 days prior to apheresis);
• Estimated survival \> 12 weeks;

You may not qualify if:

• Participants were not included in the trial if they met any of the following criteria:
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed hepatocellular-cholangiocarcinoma;
• Intrahepatic recurrence or extrahepatic metastasis, or residual hepatocellular carcinoma detected before apheresis (imaging evidence according to RECIST v1.1);
• More than 2 years since surgical resection;
• Pregnant or lactating females;
• Positive test results for any of the following: human immunodeficiency virus (HIV) antibody, Treponema pallidum antibody, hepatitis C virus (HCV) ribonucleic acid (RNA), hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) positive and hepatitis B virus deoxyribonucleic acid \[HBV DNA\] ≥ 1000 IU/mL (HBsAg-positive or HBcAb-positive participants must receive antiviral therapy), cytomegalovirus (CMV) DNA, Epstein-Barr virus (EBV) DNA;
• Any uncontrolled active infection, including but not limited to active tuberculosis, infectious diseases requiring systemic treatment, etc.; Patients who use drugs to prevent infection can be enrolled at the discretion of the investigator;
• Previous or current hepatic encephalopathy;
• Presence of clinically significant massive abdominal/pleural effusion, defined as: positive signs of pleural/peritoneal effusion on physical examination or pleural/peritoneal effusion requiring intervention (e.g., paracentesis or drug therapy) for control;
• Toxicities caused by previous treatment have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) v5.0 ≤ Grade 1, except for alopecia, pigmentation, other laboratory abnormalities that do not affect the tolerability of the participants as judged by the investigator;
• Received anti-tumor treatment for the disease under study within 2 weeks prior to apheresis, including but not limited to surgery, systemic drug therapy (or within 5 half-lives of the drug, whichever is shorter), radiotherapy, interventional therapy, etc.;
• Received immunotherapy including anti-PD-1/PD-L1, anti-CTLA-4, or any other investigational therapy within 4 weeks (or within 5 half-lives of the drug, whichever is shorter) prior to apheresis;
• Previously received any cell therapy (including CAR-T cells, TCR-T cells, TILs, etc.);
• Received systemic glucocorticoid therapy within 7 days prior to apheresis; Patients with recent or current use of inhaled or topical corticosteroids and physiologic dose replacement therapy may be enrolled;
• Vaccination with live or live attenuated vaccines within 4 weeks prior to apheresis or planned during the trial;

Sponsors & Collaborators

• CARsgen Therapeutics Co., Ltd.: lead
• Shanghai Zhongshan Hospital: collaborator

Study Sites (15)

Cancer Hospital Chinese Academy of Medical Sciences

Beijing, China

RECRUITING

Hunan Provincial People's Hospital

Changsha, China

RECRUITING

Sichuan Cancer Hospital

Chengdu, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, China

RECRUITING

Chongqing university ca cer hospital

Chongqing, China

RECRUITING

Mengchao hepatobiliary hospital of fujian medical university

Fuzhou, China

RECRUITING

Sun Yat-sen University Cancer Center

Guanzhou, China

RECRUITING

Sir Run Run Shaw Hospital Zhejiang University School of Medicine

Hangzhou, China

RECRUITING

The second affiliated hospital zhejiang university school of medicine

Hangzhou, China

RECRUITING

Zhongshan Hospital Fudan University

Shanghai, China

RECRUITING

Liaoning Cancer Hospital

Shenyang, China

RECRUITING

The first hospital of china medical university

Shenyang, China

RECRUITING

Tianjin medical university cancer hospital

Tianjin, China

RECRUITING

Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science & Technology

Wuhan, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

RECRUITING

Study Officials

• Jia fan

  Fudan University

  STUDY DIRECTOR

Central Study Contacts

Lifeng Zhang

CONTACT

86-21-54489928; lifengzhang@carsgen.com

Tianci Su

CONTACT

86-21-64501828; tiancisu@carsgen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: It is planned to enroll approximately 30 participants to receive CT011 infusion. During the trial, the sample size may be appropriately adjusted as assessed by the sponsor and the investigator.

Study Record Dates

• First Submitted: July 25, 2024
• First Posted: August 19, 2024
• Study Start: October 8, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: August 19, 2024

Record last verified: 2024-08

Locations

CN (15)