A Clinical Study of TQB2618 Injection Combined With Penpulimab Injection and Anlotinib Hydrochloride Capsules for First-line Treatment of Advanced Hepatocellular Carcinoma (HCC).

Advanced Hepatocellular Carcinoma Clinical Trial

Official title:

A Phase Ib Clinical Study to Evaluate the Efficacy and Safety of TQB2618 Injection Combined With Penpulimab Injection and Anlotinib Hydrochloride Capsules as First-line Treatment for Advanced Hepatocellular Carcinoma.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05975645
• Other study ID #: TQB2618-AK105-Ib-04
• Status: Recruiting
• Phase: Phase 1
• Start date: August 15, 2023
• Est. completion date: April 2025

Study information

• Verified date: March 2024
• Source: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
• Contact: Qiang Xia, Doctor
• Phone: +86 13661889035
• Email: Xiaqiang[@]medmail.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open, single-arm, multi-center clinical study designed to evaluate the efficacy and safety of TQB2618 injection combined with penpulimab injection and Anlotinib Hydrochloride Capsules in patients with advanced HCC.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 40
• Est. completion date: April 2025
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• 18-75 years old; Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1; Life expectancy = 3 months.

• Patients with HCC diagnosed by histopathological or cytological examination or in line with clinical diagnostic criteria.

• No systematic treatment for advanced HCC has been received before.

• China liver cancer staging (CNLC)stage III or Barcelona Clinic Liver Cancer (BCLC) stage C, or CNLC stage II (BCLC B) subjects who are not suitable for local treatment and surgical treatment, or who are judged by researchers to be unable to benefit from local treatment and surgical treatment.

• Liver function score was good.

• Hepatitis B surface antigen (HBsAg) positive patients must meet hepatitis B virus deoxyribonucleic acid (HBV DNA) quantification < 10000 IU / ml (or 50000 copy/ml), and anti-HBV therapy should be given for at least 1 week before the first administration; investigator needs to determine that hepatitis C virus (HCV) infection is in a stable state.

• Patients after local treatment should be administered at least 4 weeks after the end of local treatment and have fully recovered from treatment toxicity and/or complications.

• Radiotherapy for bone metastases accompanied by clinical symptoms must be completed at least 2 weeks before the first administration.

• Has at least one measurable lesion.

• The Main organ function is normal.

• Men and women of childbearing age should agree to use contraceptive measures (such as intrauterine devices, contraceptives, or condoms) during the study period and within 6 months after the end of the study. Serum human chorionic gonadotropin (HCG) test is not negative within 7 days before the first administration and must be non-lactating patients.

• Voluntary and signed informed consent, good compliance.

Exclusion Criteria:

• Combined disease and medical history :

1. Other malignant tumors had appeared or were suffering from at the same time within 3 years before the first administration.

2. Unrelieved toxic reactions higher than grade 1 due to any previous treatment.

3. Major surgical treatment, obvious traumatic injury, or long-term unhealed wounds or fractures were received within 28 days before the first administration.

4. Patients who had any bleeding or bleeding events =grade 3 within 8 weeks before the first administration, or had arterial/venous thrombosis events within 6 months before the first administration.

5. There was a history of gastrointestinal bleeding within 6 months before the first administration; other conditions that may cause gastrointestinal bleeding or perforation.

6. Patients with portal hypertension have a high risk of bleeding, or gastroscopy confirmed red sign or severe esophageal and gastric varices.

7. Active pulmonary tuberculosis, history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonia, radiation pneumonitis requiring treatment, or active pneumonia with clinical symptoms.

8. Have a history of mental drug abuse that cannot be withdrawn, or have a mental disorder.

9. Patients who had previously received or planned to receive allogeneic bone marrow transplantation or solid organ transplantation within 6 months.

10. Have a history of hepatic encephalopathy.

11. Currently using or recently used aspirin (>325mg/day) or dipyridamole, ticlopidine, clopidogrel, and cilostazol treatment.

12. Have any heavy and/or uncontrolled disease.

• Tumor-related, previous, and current treatment:

1. Histopathology or cytology confirmed as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, hepatobiliary cell carcinoma, mixed liver cancer, etc. Clinically considered as hepatobiliary mixed tumor.

2. According to imaging examination, there was portal vein tumor thrombus involving the trunk; or inferior vena cava tumor thrombus or heart involvement.

3. Subjects have been treated with immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1), Programmed cell death 1 ligand 1(PD-L1), T cell immunoglobulin and mucin domain containing protein 3 (TIM-3), etc.

4. Previously received any type of cellular immunotherapy.

5. Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage.

6. Suffering from spinal cord compression, cancerous meningitis, with symptoms of brain metastasis or symptoms control time less than 4 weeks.

• Study-related treatment:

1. There was a history of attenuated live vaccine inoculation within 28 days before the first administration, or attenuated live vaccine inoculation was planned during the study period.

2. Severe hypersensitivity reaction occurred after using macromolecular drugs.

3. Those with multiple factors affecting the oral administration of drugs.

4. Active autoimmune diseases requiring systemic treatment occurred within 2 years before the first administration.

5. immunodeficiency, or Undergoing systemic glucocorticoid therapy or any other form of immunosuppressive therapy.

• Those who participated in and used other anti-tumor clinical trial drugs within 4 weeks before the first administration.

• According to the judgment of the investigators, some situations seriously endanger the safety of the subjects or affect the subjects to complete the study.

Related Conditions & MeSH terms

• Advanced Hepatocellular Carcinoma
• Carcinoma
• Carcinoma, Hepatocellular

Intervention

Drug:
• Penpulimab injection
Penpulimab is an inhibitor of programmed cell death 1 (PD-1).
• TQB2618 injection
TQB2618 injection is an inhibitor of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3).
• Anlotinib Hydrochloride Capsules
Anlotinib hydrochloride is a muti-target tyrosine kinase inhibitor.

Locations

Country	Name	City	State
China	Hunan Cancer Hospital	Changsha	Hunan
China	The Third Affiliated Hospital of Sun Yat-sen University	Guangzhou	Guangdong
China	Affiliated Cancer Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Third Affiliated Hospital of Naval Medical University	Shanghai	Shanghai
China	The First People's Hospital of Shangqiu City	Shangqiu	Henan
China	The six people's Hospital of Shenyang	Shenyang	Liaoning
China	Gansu Wuwei Cancer Hospital	Wuwei	Gansu
China	Affiliated hospital of zunyi medical university	Zunyi	Guizhou

Sponsors (1)

Lead Sponsor	Collaborator
Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall response rate (ORR)	Percentage of subjects achieving complete response (CR) and partial response (PR).	Up to 2 years.
Secondary	Overall Survival (OS)	OS is defined as the time from the first time the subject received treatment to death due to any cause.	Up to two and a half years.
Secondary	Progress Free Survival (PFS)	The time from the first administration of the drug to disease progression or death (whichever occurs first).	Up to 2 years.
Secondary	Disease Control Rate (DCR)	Percentage of subjects achieving CR and PR and stable disease (SD) is greater than or equal to 4-6 weeks.	Up to 2 years.
Secondary	Duration of Response (DOR)	The time from the first assessment of the tumor's CR or PR to the disease's first progression or death from various causes.	Up to 2 years.
Secondary	Incidence of Anti-Drug antibody (ADA)	The incidence of ADA after the administration of TQB2618.	Before administration on the first day of the 1st, 2nd, 4th, and 8th cycles, 30 days and 90 days after the last administration. Each cycle is 21 days.
Secondary	Incidence of neutralizing antibodies (Nab)	The incidence of Nab after the administration of TQB2618.	Before administration on the first day of the 1st, 2nd, 4th, and 8th cycles, 30 days and 90 days after the last administration. Each cycle is 21 days.
Secondary	Incidence of adverse events (AEs)	All adverse medical events that occur after the subject receives the investigational drug, evaluated according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).	Baseline up to 2 years.
Secondary	Severity of adverse events (AEs)	All adverse medical events that occur after the subject receives the investigational drug, evaluated according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).	Baseline up to 2 years.
Secondary	Incidence of Serious adverse events (SAEs)	It refers to adverse medical events such as death, life-threatening, permanent, or serious disability or loss of function, hospitalization or prolonged hospitalization, and congenital abnormalities or birth defects after the subject receives the experimental drug.	Baseline up to 2 years.