Clinical trial NCT05352542: GPC3-targeting CART Cell in Treatment of Advanced Hepatocellular Carcinoma
Official title: A Phase I Clinical Trial for Evaluating the Safety, Tolerance and Efficacy of GPC3-targeting CART Cell in Treatment of Advanced Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Advanced Hepatocellular Carcinoma
Lead sponsor: The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
Sponsor class: OTHER
First posted: 2022-04-29
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Phase I Clinical Trial for Evaluating the Safety, Tolerance and Efficacy of GPC3-targeting CART Cell in Treatment of Advanced Hepatocellular Carcinoma

Detailed description: This is an open-label, dose escalation/expansion study to assess the safety, tolerability, and efficacy of CART cell in patients ≥ 18 years of age with relapsed or refractory advanced hepatocellular carcinoma. Patients who meet the eligibility criteria will receive cell infusion. The study will include the following sequential phases: screening, pre-treatment (cell product preparation; lymphodepleting chemotherapy), treatment and follow up

Eligibility criteria: Inclusion Criteria:

1. Subjects have fully understood the possible risks and benefits of participating in this study, are willing to follow and able to complete all trial procedures, and have signed informed consent;
2. Age 18-75 years;
3. Patients diagnosed as advanced hepatocellular carcinoma (HCC) histopathologically or cytologically; Progression or intolerance after previous standard systemic therapy;
4. GPC3 is detected positive by immunohistochemistry (IHC);
5. Child-Pugh score ≤ 7;
6. At least one assessable tumor lesion;
7. ECOG score: 0-1;
8. Expected survival ≥ 3 months;
9. Clinical laboratory values meet screening visit criteria

Exclusion Criteria:

1. Previous CAR-T cell, TCR-T cell or other cell therapies or therapeutic tumor vaccination directed at any target;
2. Any previous GPC3 targeted therapy;
3. Prior antitumor therapy with insufficient washout period;
4. Brain metastases with central nervous system symptoms;
5. Pregnant or lactating women
6. HCV-Ab or/and HIV-Ab positive; active syphilis;
7. Severe underlying diseases
8. Any condition that, in the opinion of the investigator, will make the subject unsuitable for participation in this study.

Primary outcomes:
measure: Incidence, severity, and type of treatment-emergent adverse events (TEAEs)
timeFrame: Minimum 2 years after CART infusion (Day 1)
measure: Dose-limiting toxicity (DLT) rate
timeFrame: Minimum 2 years after CART infusion (Day 1)
measure: Recommended Phase 2 dose (RP2D) finding
timeFrame: 30 days after CART infusion (Day 1)
measure: CAR positive T cells
timeFrame: Minimum 2 years after CART infusion (Day 1)
measure: CAR transgene levels in peripheral blood
timeFrame: Minimum 2 years after CART infusion (Day 1)
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: Minimum 2 years after CART infusion (Day 1)
measure: Disease control rate (DCR)
timeFrame: Minimum 2 years after CART infusion (Day 1)
measure: Duration of Response(DoR)
timeFrame: Minimum 2 years after CART infusion (Day 1)
measure: Time to Response (TTR)
timeFrame: Minimum 2 years after CART infusion (Day 1)
measure: Progress Free Survival (PFS)
timeFrame: 2 years after CART infusion (Day 1)
measure: Overall Survival (OS)
timeFrame: Minimum 2 years after CART infusion (Day 1)
measure: Incidence of anti-CART antibody
timeFrame: Minimum 2 years after CART infusion (Day 1)
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Gobroad Boren Hospital
state: Beijing
city: Beijing
country: China
facility: Chinese PLA General Hospital
state: Beijing
Study officials:
References: