Cadonilimab in Combination With Lenvatinib and Hepatic Arterial Infusion Chemotherapy (HAIC) for the Treatment of Unresectable Hepatocellular Carcinoma

NCT06406634 | Recruiting Phase 2

• 1 other identifier: AK104-IIT-C-M-0035
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an open-label, multicenter, single-arm Phase II clinical study to evaluate the effectiveness of Cadonilimab(AK104) in Combination With Lenvatinib and Hepatic Arterial Infusion Chemotherapy (HAIC) for the Treatment of Unresectable Hepatocellular Carcinoma

Conditions

Hepatocellular Carcinoma

Keywords

Cadonilimab; Lenvatinib; Hepatic Arterial Infusion Chemotherapy (HAIC); Unresectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate

  ORR is the proportion of patients with best response of complete response (CR) and PR

  from the first drug administration up to two years

Secondary Outcomes (5)

• Progression-free Survival (PFS)

  Time Frame: from the first drug administration up to two years

• Disease Control Rate (DCR)

  from the first drug administration up to two years

• Duration of Response(DOR)

  from the first drug administration up to two years

• Overall Survival(OS)

  from the first drug administration up to two years

• Adverse event (AE)

  From the subject signs the ICF to 90 days after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first

Study Arms (1)

Experimental: Cadonilimab +Lenvatinib+Hepatic Arterial Infusion Chemotherapy (HAIC)

EXPERIMENTAL

HAIC(FOLFOX)+Cadonilimab (AK104) (10 mg/kg, Q3W, iv) + Lenvatinib (8 mg (if patient body weight was \<60 kg) or 12 mg (if patient body weight was ≥60 kg) )

Drug: Cadonilimab; Drug: Lenvatinib

Interventions

Cadonilimab DRUG

Injectable solution

Also known as: AK104

Experimental: Cadonilimab +Lenvatinib+Hepatic Arterial Infusion Chemotherapy (HAIC)

Lenvatinib DRUG

capsule

Experimental: Cadonilimab +Lenvatinib+Hepatic Arterial Infusion Chemotherapy (HAIC)

Eligibility Criteria

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

You may qualify if:

• The written informed consent form should be signed before a subject participates in the trial；
• Histologically/cytologically confirmed HCC or cirrhosis meeting the clinical diagnostic criteria of HCC by the American Association for the Study of Liver Diseases (AASLD)；
• According to the Chinese Guidelines for Diagnosis and Treatment of Primary Liver Cancer (2022 edition), eligible for China liver cancer staging (CNLC) Stage IIIa and is not suitable for radical treatment, such as resection, ablation, or liver transplantation. Suitable for HAIC surgery and chemotherapy drugs prescribed in advance by the research center, without any contraindications to HAIC surgery and chemotherapy drugs；
• Child-Pugh A or B；
• at least 1 measurable lesion according to RECIST v1.1；
• Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0 or 1；
• Adequate organ and marrow function, as defined below； 1) Absolute neutrophil count (ANC) ≥1.5x109/L without granulocyte colony-stimulating factor in the last 14 days； 2) Platelets ≥75×109/L without transfusion in the last 14 days； 3) Hemoglobin ≥8.5 g/dL without transfusion or erythropoietin use in the last 14 days； 4) Serum total bilirubin (TBL) ≤2 × ULN； 5) AST and ALT ≤5× ULN； 6) Serum creatinine ≤1.5 × upper limit of normal (ULN)； Urine protein ≤(++) , or 24-hour urine protein quantification less than 1 g； 7) Good coagulation, defined as the international normalized ratio (INR) ≤ 2， or activated partial prothrombin time (PT) ≤ 1.5 times ULN；
• a woman of childbearing potential (WOCBP) who is sexually active with a nonsterilized male partner must have a negative pregnancy test at the Screening visit (within 3 days before the first dose of the investigational product \[Cycle 1 Day 1\]). If a negative urine pregnancy test result cannot be confirmed, a blood pregnancy test will be requested. Females not of childbearing age were defined as being at least 1 year postmenopausal or having undergone surgical sterilization or hysterectomy；
• If there is a risk of conception, all subjects (male or female) will be required to use contraception with an annual failure rate of less than 1% for the entire treatment period up to 120 days after administration of the study drug at the end of treatment；

You may not qualify if:

• Containing components such as fibrolamellar hepatocellular carcinoma, sarcomatoid hepatocellular carcinoma, and cholangiocarcinoma that have been previously confirmed by histology/cytology;
• Recurrence of previous hepatocellular carcinoma；
• Autoimmune hepatitis (requires liver puncture)
• Have a history of hepatic encephalopathy or liver transplantation;
• Diffuse liver cancer;
• Symptomatic pleural effusion, ascites, and pericardial effusion that require drainage;
• History of kidney disease or nephrotic syndrome;
• Presence of bleeding events from esophageal or gastric varices caused by portal hypertension within the past 6 months. Presence of known severe (G3) varicose veins in endoscopy within 3 months before the first dose. Evidence of portal hypertension (including the finding of splenomegaly in imaging studies) with a high risk of bleeding assessed by the investigator;
• Any arterial/venous thromboembolic events within 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient cerebral ischemic attack, pulmonary embolism, deep vein thrombosis, or any other history of serious thromboembolism. Presence of implantable venous port or catheter-derived thrombosis, or superficial venous thrombosis, barring stable thrombosis following the conventional anticoagulation treatment. Prophylactic use of low-dose low-molecular-weight heparin is permitted;
• Presence of any life-threatening bleeding events;
• consecutive dosing of aspirin or other drugs, e.g., dipyridamole and clopidogrel, known to inhibit the platelet function before the first dose;
• Uncontrolled hypertension (systolic greater than 140 mmHg or diastolic greater than 90 mmHg) after the optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy.
• Symptomatic congestive cardiac failure (NYHA Class II-IV). Symptomatic or poorly controlled arrhythmia. History of congenital long QT syndrome or corrected Qtc \> 500 ms (calculated using Fridericia formula) during screening.
• History of gastrointestinal perforation and/or fistula, history of bowel obstruction (including incomplete bowel obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection accompanied with chronic diarrhea), Crohn's disease, ulcerative colitis, or chronic diarrhea within the past 6 months.
• Receipt of major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks before the first dose or having unhealed wounds, ulcers, or fractures. Receipt of tissue biopsy or other minor surgeries within 7 days before the first dose, barring venipuncture and catheterization for intravenous infusion.

Sponsors & Collaborators

• Hunan Cancer Hospital: lead

Study Sites (1)

Hunan Cancer Hospital

Changsha, Hunan, 410013, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

lenvatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2024
• First Posted: May 9, 2024
• Study Start: May 15, 2024
• Primary Completion: April 20, 2026
• Study Completion (Estimated): April 20, 2027
• Last Updated: May 9, 2024

Record last verified: 2024-05

Locations

CN (1)