Clinical trial NCT05975645: A Clinical Study of TQB2618 Injection Combined With Penpulimab Injection and Anlotinib Hydrochloride Capsules for First-line Treatment of Advanced Hepatocellular Carcinoma (HCC).
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.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Hepatocellular Carcinoma
Lead sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-08-04
Enrollment: 40
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: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: Up to 2 years.
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Up to two and a half years.
measure: Progress Free Survival (PFS)
timeFrame: Up to 2 years.
measure: Disease Control Rate (DCR)
timeFrame: Up to 2 years.
measure: Duration of Response (DOR)
timeFrame: Up to 2 years.
measure: Incidence of Anti-Drug antibody (ADA)
timeFrame: 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.
measure: Incidence of neutralizing antibodies (Nab)
timeFrame: 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.
measure: Incidence of adverse events (AEs)
timeFrame: Baseline up to 2 years.
measure: Severity of adverse events (AEs)
timeFrame: Baseline up to 2 years.
measure: Incidence of Serious adverse events (SAEs)
timeFrame: Baseline up to 2 years.
Other outcomes:
Locations:
city: Wuwei
country: China
facility: Gansu Wuwei Cancer Hospital
state: Gansu
city: Guangzhou
country: China
facility: The Third Affiliated Hospital of Sun Yat-sen University
state: Guangdong
city: Zunyi
country: China
facility: Affiliated hospital of zunyi medical university
state: Guizhou
city: Harbin
country: China
facility: Affiliated Cancer Hospital of Harbin Medical University
state: Heilongjiang
city: Shangqiu
country: China
facility: The First People's Hospital of Shangqiu City
state: Henan
city: Changsha
country: China
facility: Hunan Cancer Hospital
state: Hunan
city: Shenyang
country: China
facility: The six people's Hospital of Shenyang
state: Liaoning
city: Shanghai
country: China
facility: Third Affiliated Hospital of Naval Medical University
state: Shanghai
Study officials:
References: