Anlotinib + Benmelstobart + HAIC in Unresectable HCC: A Phase II Study

NCT07806292 | Recruiting Phase 2

• 2 other identifiers: SYSKY-2025-230-06ChiCTR2600128357
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To evaluate the efficacy and safety of anlotinib combined with benmelstobart and HAIC as first-line treatment for unresectable hepatocellular carcinoma.

Conditions

Unresectable Hepatocellular Carcinoma

Keywords

anlotinib; benmelstobart; HAIC; unresectable hepatocellular carcinoma

Outcome Measures

Primary Outcomes (1)

• objective response rate (ORR)

  ORR as assessed by the investigator using RECIST v1.1 criteria

  12 months

Secondary Outcomes (4)

• ORR (mRECIST)

  12 months

• progression free survival (PFS)

  up to 24 months

• overall survival (OS)

  up to 24 months

• Surgical conversion rate

  up to 12 months

Study Arms (1)

Experimental: anlotinib combined with benmelstobart and HAIC

EXPERIMENTAL

Drug: anlotinib combined with benmelstobart and HAIC

Interventions

anlotinib combined with benmelstobart and HAIC DRUG

HAIC with FOLFOX (oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-fluorouracil 400 mg/m² bolus followed by 2400 mg/m² over 23 h) plus oral anlotinib 10 mg (d1-14) and intravenous benmelstobart 1200 mg (d1) every 3 weeks

Experimental: anlotinib combined with benmelstobart and 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:

• Age between 18 and 75 years, regardless of gender.
• Confirmed diagnosis of unresectable hepatocellular carcinoma (HCC) according to both the China Liver Cancer (CNLC) staging criteria and the American Association for the Study of Liver Diseases (AASLD) clinical diagnostic criteria.
• At least one measurable lesion as defined by the following criteria: the longest diameter ≥ 10 mm for non-nodal lesions, or the short-axis diameter ≥ 15 mm for nodal lesions; confirmed unresectable HCC; Child-Pugh liver function score ≤ 7.
• Naive to any local (ablation, hepatic arterial embolization/infusion therapy, liver transplantation) or systemic therapy (chemotherapy and/or molecular targeted therapy, immunotherapy; antiviral therapy excluded) for HCC at initial diagnosis, or patients with intrahepatic recurrence after previous radical resection.
• Expected survival time ≥ 12 weeks.
• No anti-HCC drugs (including modern traditional Chinese medicine preparations indicated for HCC: Lentinan Injection, Kanglaite Injection or Soft Capsules, Aidi or Kangsaidi Injection, Propaneed Oil, Huai'er Granules, and Ganfule Tablets) administered within 2 weeks prior to the first dose.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.
• HBV DNA \< 10\^4 copies/ml (2000 IU/ml). If HBV DNA ≥ 10\^4 copies/ml, antiviral therapy must be initiated first and continued until HBV DNA drops below 10\^4 copies/ml before entering the study, along with ongoing antiviral medication and monitoring of liver function and HBV viral load.
• Normal function of major organs, meeting the following criteria:
• a) Hematology (no blood transfusion or G-CSF administered within 14 days prior to screening): i. Hemoglobin (Hb) ≥ 90 g/L; ii. Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; iii. Platelet count (PLT) ≥ 75 × 10\^9/L; b) Biochemistry (no albumin (ALB) administration within 14 days prior to testing): i. Albumin (ALB) ≥ 28 g/L; ii. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 5.0 × upper limit of normal (ULN); iii. Total bilirubin (TBIL) ≤ 4.0 × ULN (patients with obstructive jaundice may be enrolled after percutaneous transhepatic cholangial drainage (PTCD)); iv. Creatinine ≤ 1.5 × ULN; v. Electrolytes essentially normal or normalized after treatment. c) Urinalysis: i. Urine protein ≤ 1+.
• The patient voluntarily consents to enrollment, signs the written informed consent form (ICF), and is able to comply with the required treatment and follow-up visits according to the protocol.

You may not qualify if:

• Histologically confirmed fibrolamellar HCC, sarcomatoid HCC, or combined hepatocellular-cholangiocarcinoma (HCC-ICC).
• Symptomatic moderate to massive pleural effusion/ascites.
• Obstructive jaundice, liver failure, or hepatic encephalopathy.
• Patients with a second primary cancer or multiple malignancies, except for HCC, carcinoma in situ of the cervix, and non-melanoma skin cancer, or a history of other malignancies previously diagnosed and explicitly cured for at least 5 years with no evidence of subsequent recurrence.
• Active bleeding or coagulation abnormalities (Prothrombin Time, PT \> 16 s; Activated Partial Thromboplastin Time, APTT \> 43 s; International Normalized Ratio, INR ≥ 2), bleeding tendency, or currently receiving thrombolytic, anticoagulant, or antiplatelet therapy.
• Concomitant use of medications that may prolong the QTc interval and/or induce Torsades de Pointes (TdP), or affect the metabolism of chemotherapeutic agents.
• Pregnant or lactating women; sexually active men or women of childbearing potential who are unwilling or unable to use effective contraception.
• Any significant clinical or laboratory abnormalities that, in the opinion of the investigator, would affect the safety evaluation, such as: uncontrolled active infection (\> NCI-CTCAE v5.0 Grade 2), uncontrolled diabetes (\> NCI-CTCAE v5.0 Grade 2), hypertension not controlled to below the specified range (systolic blood pressure \< 140 mmHg and diastolic blood pressure \< 90 mmHg) despite treatment with two or more antihypertensive drugs, peripheral neuropathy ≥ Grade 2 (NCI-CTCAE v5.0), congestive heart failure ≥ Grade 2 (NCI-CTCAE v5.0), myocardial infarction within 6 months, or thyroid dysfunction (\> NCI-CTCAE v5.0 Grade 2), etc.
• History of brain metastases, subdural metastasis, or severe mental illness; patients suspected of central nervous system (CNS) metastases must be excluded by cranial MRI.
• History of gastrointestinal bleeding or definite predisposition to gastrointestinal bleeding within the past 3 months, such as known active ulcer lesions, or fecal occult blood ≥ ++ (not eligible for enrollment); if persistent fecal occult blood is positive, a gastroscopy examination is required.
• Severe gastric fundus/esophageal wall varices requiring interventional treatment.
• Occurrence of abdominal or gastrointestinal perforation or intra-abdominal abscess within 4 weeks prior to the first dose.
• Significant abnormality in glomerular filtration rate (estimated creatinine clearance \< 60 ml/min or serum creatinine \> 1.5 × ULN).
• Active hepatitis C (i.e., anti-HCV positive or HCV-RNA positive with abnormal liver function); known history of HIV infection.
• Receipt of other investigational drugs or medical devices within 4 weeks prior to the first dose; or prior use of anti-tumor indicated drugs where less than 2 weeks or 5 drug half-lives (whichever is longer) have elapsed between the completion of previous treatment and the administration of the study drug, and adverse events caused by prior treatment have not recovered to ≤ CTCAE Grade 1.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Guangzhou, Guangdong, China

RECRUITING

Central Study Contacts

Changzhen Shang, M.D, PhD

CONTACT

+86-20-3407 0701; shchzh2@mail.sysu.edu.cn

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: September 2, 2026
• First Posted: September 8, 2026
• Study Start: April 28, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): April 28, 2027
• Last Updated: September 8, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)