Benmelstobart Plus Anlotinib Combined With SBRT for Patients With Hepatocellular Carcinoma Failing First-Line Targeted Therapy

NCT07537777 | Not Yet Recruiting Phase 2

• 1 other identifier: NFEC-2025-759
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

This prospective, single-arm, multicenter Phase II clinical trial aims to evaluate the efficacy and safety of Benmelstobart plus anlotinib combined with SBRT in patients with oligometastatic hepatocellular carcinoma who have failed first-line targeted therapy. Key study questions include: What is the progression-free survival (PFS) for patients treated with this regimen? How do the objective response rate (ORR), disease control rate (DCR), and overall survival (OS) compare? What are the safety and tolerability profiles of the combination therapy? Eligible subjects (after signing informed consent) will receive anlotinib 10mg on days 1-14 every 3 weeks + Benmelstobart 1200mg on day 1 every 3 weeks + SBRT. Treatment cycles will be 3 weeks long, continuing until a protocol-specified treatment discontinuation event occurs. Following treatment completion, subjects will undergo post-treatment safety follow-up and survival monitoring, with tumor progression monitoring conducted post-treatment.

Conditions

Oligometastatic Hepatocellular Carcinoma; Benmelstobart; Anlotinib; SBRT; Hepatocellular Carcinoma (HCC); First-line Targeted Therapy Failure

Outcome Measures

Primary Outcomes (1)

• Progression free survival time (PFS)

  Baseline（day 1), and after every two treatment cycles（up to 2 years).

Secondary Outcomes (4)

• Objective response rate (ORR)

  Baseline（day 1), and after every two treatment cycles（up to 2 years).

• The disease control rate (DCR)

  Baseline（day 1), and after every two treatment cycles（up to 2 years).

• Overall survival time (OS)

  Baseline（day 1), and after every two treatment cycles（up to 2 years).

• Treatment-Emergent Adverse Events (Safety and Tolerability)

  Throughout the entire treatment period and 30 days after the last dose

Study Arms (1)

Benmelstobart Plus Anlotinib Combined With SBRT

EXPERIMENTAL

Drug: Benmelstobart; Procedure: SBRT; Drug: Anlotinib

Interventions

Benmelstobart DRUG

Benmelstobart will be administered at a dose of 1200mg on day 1 via intravenous infusion, once every 3 weeks. The maximum cumulative treatment duration shall be 2 years.

Benmelstobart Plus Anlotinib Combined With SBRT

SBRT PROCEDURE

SBRT 50Gy/5F

Benmelstobart Plus Anlotinib Combined With SBRT

Anlotinib DRUG

Aronitin 10mg orally on days 1-14 every 3 weeks, with one treatment cycle defined as 3 weeks. The maximum cumulative treatment duration shall be 2 years.

Benmelstobart Plus Anlotinib Combined With SBRT

Eligibility Criteria

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

You may qualify if:

• The patients voluntarily participated in the study, signed the informed consent form, and the compliance was good.
• Age \>=18 years old, male or female;
• Patients with histologically confirmed or clinically diagnosed HCC, and the disease is not suitable for radical surgery;
• Patients with oligometastatic HCC who had failed previous target-immunotherapy combined with first-line therapy. Oligometastases are defined as the number of metastatic organs ≤2 and the total number of metastases \<=5, and oligometastases are suitable for SBRT treatment.
• Child-Pugh liver function score \<=7;
• ECOG score of 0-1;
• Expected survival time before initiation of study drug \>=12 weeks;
• At least one measurable lesion (the long diameter of the measurable lesion on enhanced spiral CT or enhanced MR Scan \>=10mm or the short diameter of the enlarged lymph node \>=15mm according to RECISTv1.1; a lesion that has been treated with previous radiotherapy can be considered as a target lesion after definite progression according to RECISTv1.1 criteria);
• The following laboratory tests performed within 7 days before the first dose of medication confirmed that the patient's bone marrow, liver and kidney function met the following requirements for study participation: 1) hemoglobin \>=80 g/L (which can be maintained or exceeded by transfusion); 2) absolute neutrophil count (ANC) \>=1.5×10\^9; 3) platelet count \>=50×10\^9/mm3; 4) Total bilirubin \<=1.5 times upper limit of normal; 5) alanine aminotransferase and aspartate aminotransferase \<=2.5 times upper limit of normal (ULN); 6) creatinine \<=1.5 times upper limit of normal (ULN); And creatinine clearance \>=60ml/min; 7) international normalized ratio (INR) of prothrombin time \<=1.5 in patients without previous anticoagulant therapy; Partial thromboplastin time (APTT)\<=1.5 times the upper limit of normal; 8) if HBV-DNA is detectable, antiviral therapy should be started before enrollment; 9) If HCV-RNA is detectable, antiviral therapy should be started before enrollment.
• Women of childbearing age: must agree to abstain from sexual intercourse (heterosexual intercourse) or use a reliable, effective method of contraception for at least 120 days from the time of written informed consent until the last dose of study drug is administered. A serum HCG test had to be negative within 7 days before starting study treatment; And they must be non-lactating. Women were considered to be fertile if they had menstruated, had not yet reached a postmenopausal state (\>=12 months of continuous absence of menses, with no cause other than menopause identified), and had not undergone sterilization procedures (e.g., hysterectomy, bilateral tubal ligation, or bilateral oophorectomy).
• Male patients whose partner was a woman of reproductive age had to agree to abstain from sex or to use a reliable, effective method of contraception for at least 120 days from the time of written informed consent until the last dose of study drug was administered. Male patients also had to agree not to donate sperm during the same period. Male subjects whose partner was pregnant were required to use condoms.

You may not qualify if:

• Known cholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma, and fibrolamellar cell carcinoma. Other active malignant tumors other than HCC within 5 years or at the same time. The cured localized tumors, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, prostate cancer in situ, cervical cancer in situ, breast cancer in situ, etc., were excluded.
• Prior receipt of anlotinib or a non-PD-1 monoclonal antibody immune checkpoint inhibitor;
• The time interval between the last target-free drug use and enrollment was less than 3 weeks.
• Patients who received previous local treatment (including TACE, ablation, HAIC, or radiotherapy) for the target lesion less than 1 month before enrollment.
• Patients preparing for or previously receiving organ or allogeneic bone marrow transplantation;
• Moderate or severe ascites with clinical symptoms, which required therapeutic puncture, drainage or Child-Pugh score \>2 (except for patients with small amount of ascites on imaging but without clinical symptoms); Uncontrolled or moderate or above amount of pleural effusion and pericardial effusion;
• A history of gastrointestinal bleeding within 6 months before the initiation of study treatment or a definite tendency for gastrointestinal bleeding, such as: Patients with risk of bleeding or severe esophagogastric varices, local active gastrointestinal ulcer lesions, and persistent positive fecal occult blood were excluded (patients with positive fecal occult blood at baseline could be re-examined, and patients with positive fecal occult blood after re-examination required gastroduodenoscopy (EGD). Patients with esophagogastric varices with a risk of bleeding were excluded).
• Abdominal fistula, gastrointestinal perforation, or abdominal abscess within 6 months before study treatment;
• Known inherited or acquired bleeding (e.g., coagulopathy) or thrombophilia, as in hemophilia patients;
• Current or recent (within 10 days before initiation of study treatment) use of a full-dose oral or injectable anticoagulant or thrombolytic agent for therapeutic purposes (prophylactic use of low-dose aspirin and low-molecular-weight heparin was allowed);
• Currently using or recently using (within 10 days before initiation of study treatment) aspirin (\> 325 mg/ day (maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel, and cilostazol; Thrombotic or embolic events, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), pulmonary embolism, etc., occurred within 6 months before the initiation of study treatment;
• There are not well controlled cardiac clinical symptoms or diseases, such as: (1) according to the New York Heart Association (NYHA) criteria (see Annex 5) grade II or higher cardiac dysfunction or cardiac ultrasound examination: Left ventricular ejection fraction (LVEF) \<50% (2) unstable heartache (3) myocardial infarction within 1 year before study treatment (4) clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention (5) QTc \> 450ms (male); QTc \> 470ms (female) (QTc interval was calculated with Fridericia's formula; if QTc was abnormal, three consecutive tests could be performed at a 2-minute interval, and the mean value was calculated);
• Hypertension that is not well controlled with antihypertensive medication (systolic blood pressure \>=140 mmHg or diastolic blood pressure ≥90 mmHg) (based on the mean of \>=2 readings), and the use of antihypertensive treatment to achieve these parameters is permitted; A history of hypertensive crisis or hypertensive encephalopathy;
• Major vascular disease within 6 months before starting study treatment (e.g., aortic aneurysm requiring manual repair or recent peripheral artery thrombosis);
• Severe, unhealed or dehiscence wounds and active ulcers or untreated bone fractures;

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead

Study Sites (1)

Nanfang Hospital of Southern Medical University

Guangzhou, Guangdong, 510515, China

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

anlotinib

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 Officials

• Chen Jinzhang

  Nanfang Hospital, Southern Medical University

  STUDY DIRECTOR

Central Study Contacts

Li Qi

CONTACT

86-020-62787430; nfdoctorlee@126.com

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 1, 2026
• First Posted: April 17, 2026
• Study Start: April 20, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)