Safety and Efficacy of Paclitaxel Liposome Arterial Infusion Combined With Systemic Therapy for Second-Line Treatment of Advanced Liver Cancer

A Phase Ib/II Clinical Trial to Evaluate the Safety and Efficacy of Transcatheter Arterial Infusion of Paclitaxel Cationic Liposome Combined With Systemic Therapy in Participants With Advanced Hepatocellular Carcinoma for Second-line Treatment

This trial is an open-label, dose-escalation, and randomized controlled Phase Ib/II clinical study for second-line treatment in participants with advanced hepatocellular carcinoma (HCC). Its primary objective is to evaluate the safety, tolerability, pharmacokinetic profiles, and efficacy of transcatheter arterial infusion of HA131 combined with systemic therapy in the second-line treatment of participants with advanced HCC.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Hepatocellular Carcinoma (HCC)
• Intervention / Treatment: Drug: Enlonstobart Injection; Drug: Lenvatinib Mesilate Capsules; Drug: HA131; Drug: Pembrolizumab Injection

• Study Type: Interventional
• Enrollment (Estimated): 116
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Clinical Trials Information Group officer; Phone Number: 86-0311-69085587; Email: ctr-contact@cspc.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1.Aged 18 to 75 years (inclusive), regardless of gender;
• 2.Diagnosed with hepatocellular carcinoma (HCC) by histopathology, cytology, or imaging;
• 3.HCC classified as B/C stage per BCLC (Barcelona Clinic Liver Cancer) staging system, or IIb/IIIa/IIIb stage as defined in Clinical Practice Guidelines for Primary Liver Cancer (2024 Edition) (organized by the Guidelines Committee of the Chinese Society of Clinical Oncology, 2024);
• 4.Child-Pugh liver function class ≤ 7 points within 7 days prior to the first dose administration;
• 5.Progressive disease after prior first-line systemic antineoplastic therapy containing PD-1/PD-L1 monoclonal antibody;
• 6.At least one measurable lesion at the hepatic arterial infusion site per RECIST (Response Evaluation Criteria in Solid Tumors) Version 1.1 (lesion longest diameter ≥ 1 cm; lesions that have not received prior local therapy, or lesions that progressed again after local therapy);
• 7.ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) score: 0-1.
• 8.Controlled hypertension, with blood pressure ≤ 150/90 mmHg and no changes to the antihypertensive regimen within one week prior to screening;
• 9.Estimated survival time of more than 3 months;
• 10.Before randomization, major organ/system functions are basically normal, meeting the criteria as assessed by laboratory tests.
• 11.Eligible individuals of childbearing potential (both males and females) must agree to use reliable contraceptive methods (hormonal contraceptives, barrier methods, or abstinence) with their partners during the trial and for at least 6 months after the last dose; female individuals of childbearing age must have a negative serum pregnancy test within 7 days before enrollment;
• 12.Participants must be informed about the study prior to the trial and voluntarily sign a written informed consent form.

Exclusion Criteria:

• 1.Pathologically confirmed fibrolamellar hepatocellular carcinoma (HCC), sarcomatoid HCC, cholangiocellular carcinoma, or combined hepatocellular-cholangiocarcinoma;
• 2.History of liver surgery and/or local treatment for HCC within 4 weeks prior to the first dose;
• 3.Previous antineoplastic treatment with lenvatinib;
• 4.Use of traditional Chinese medicine (TCM) preparations with indicated efficacy for anti-HCC within 14 days prior to the first dose; having received immune checkpoint inhibitors within 28 days prior to the first dose.
• 5.Active brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression;
• 6.Adverse reactions from previous antineoplastic treatment that have not resolved to ≤ Grade 1 per NCI-CTCAE Version 5.0 (except for toxicities such as alopecia that are deemed to pose no safety risks by the investigator);
• 7.Contraindications to transcatheter arterial infusion interventional surgery; known contraindications or severe allergic reactions to any component of lenvatinib, PD-1/PD-L1 monoclonal antibody, paclitaxel, or cationic liposomes;
• 8.Malabsorption syndrome or inability to take oral medications due to other reasons;
• 9.Need for administration of strong inducers or strong inhibitors of CYP2C8 and CYP3A4 within 2 weeks prior to the first study treatment or during the treatment period;
• 10.Active infection within 2 weeks prior to the first dose; presence of peripheral neuropathy of Grade II or higher (per NCI-CTCAE Version 5.0);
• 11.History of autoimmune disease, immunodeficiency, other acquired or congenital immunodeficiency diseases, or current use of immunosuppressants;
• 12.Untreated active hepatitis B.
• 13.Participants positive for anti-hepatitis C virus antibody (HCV-Ab) with HCV-RNA level above the lower limit of the central laboratory's detection range;
• 14.Participants with active syphilis;
• 15.A history of past or current hepatic encephalopathy;
• 16.Presence of ascites detectable on physical examination, ascites causing clinical symptoms, or ascites requiring special management during screening. Uncontrolled pleural effusion or pericardial effusion during screening;
• 17.Active gastrointestinal bleeding or a documented history of gastrointestinal bleeding within 6 months before the first dose; history of gastrointestinal perforation and/or fistula, or history of gastrointestinal obstruction within 6 months before the first dose;
• 18.History of major surgery within 4 weeks before the first dose (procedures such as central venous catheterization, needle biopsy, and feeding tube placement are not considered major surgery);
• 19.History of solid organ or hematopoietic stem cell transplantation;
• 20.Past or current non-infectious pneumonia/interstitial lung disease requiring systemic glucocorticoid treatment;

• 21.Cardiac dysfunction, including:

  1. Diagnosis of long QT syndrome, or QTcF (corrected QT interval using Fridericia's formula) ≥ 450 ms in males and ≥ 470 ms in females during screening (only one ECG recheck is permitted during screening, with the result of the last ECG in the screening period taken as final);
  2. High-grade atrioventricular block;
  3. Malignant arrhythmia poorly controlled by medication;
  4. History of chronic heart failure with NYHA (New York Heart Association) functional class ≥ 3;
  5. Severe valvular heart regurgitation or stenosis requiring treatment;
  6. Acute coronary syndrome or severe myocardial disease (including primary cardiomyopathy and other severe myocardial diseases assessed by the investigator) within 6 months prior to screening; severe pericardial disease (including acute pericarditis, constrictive pericarditis and other severe pericardial diseases assessed by the investigator) within 6 months prior to screening;
  7. Left ventricular ejection fraction (LVEF) < 50% as indicated by echocardiography;
• 22.History of severe neurological or psychiatric disorders (including epilepsy or dementia) that affect trial compliance;
• 23.Limb vascular thrombosis with potential severe consequences detected by ultrasound during screening; or history of thromboembolic events within 12 months prior to enrollment;
• 24.Participants with severe bleeding tendency, or history of major bleeding events within the past 6 months (e.g., previous intracranial hemorrhage, gastrointestinal bleeding, or purpura);
• 25.Urinary protein ≥ 1 g/24 h. Participants with proteinuria > 1+ on urinalysis will undergo 24-hour urine collection for quantitative assessment of proteinuria;
• 26.Other conditions deemed by the investigator to potentially increase participant risk or interfere with trial results.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase Ib Cohort 1; Lenvatinib combined with elonstobart.	Drug: Enlonstobart Injection; Administered via intravenous infusion.; Drug: Lenvatinib Mesilate Capsules; Administered orally.
Experimental: Phase Ib Cohort 2; Transcatheter arterial infusion of HA131 combined with systemic therapy (lenvatinib with pembrolizumab).	Drug: Lenvatinib Mesilate Capsules; Administered orally.; Drug: HA131; Phase Ib: Dose escalation. Phase II: Administration at the RP2D dose determined in Phase Ib. Transcatheter Arterial Infusion.; Drug: Pembrolizumab Injection; Administered via intravenous infusion.
Experimental: Phase Ib Cohort 3; Transcatheter arterial infusion of HA131 combined with systemic therapy (lenvatinib with elonstobart )	Drug: Enlonstobart Injection; Administered via intravenous infusion.; Drug: Lenvatinib Mesilate Capsules; Administered orally.; Drug: HA131; Phase Ib: Dose escalation. Phase II: Administration at the RP2D dose determined in Phase Ib. Transcatheter Arterial Infusion.
Experimental: Phase II Experimental Arm; Transcatheter arterial infusion of HA131 combined with systemic therapy (lenvatinib with or without elonstobart ).	Drug: Enlonstobart Injection; Administered via intravenous infusion.; Drug: Lenvatinib Mesilate Capsules; Administered orally.; Drug: HA131; Phase Ib: Dose escalation. Phase II: Administration at the RP2D dose determined in Phase Ib. Transcatheter Arterial Infusion.
Active Comparator: Phase II Control Arm; Systemic therapy alone (lenvatinib with or without elonstobart ).	Drug: Enlonstobart Injection; Administered via intravenous infusion.; Drug: Lenvatinib Mesilate Capsules; Administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib-DLT	Incidence of Dose-Limiting Toxicity	3years
Phase Ib- AE	Adverse Event	3years
Phase II- ORR	Overall Response Rate	3years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase Ib- ORR	Overall Response Rate	3years
Phase Ib- DCR	Disease Control Rate	3years
Phase Ib- DoR	Duration of Response	3years
Phase Ib- TTR	Time to Response	3years
Phase Ib-PFS	Progression-Free Survival	3years
Phase Ib- OS	Overall Survival	3years
Phase Ib-PK：plasma concentration of Paclitaxel, DOTAP, Enlonstobart	Pharmacokinetics：plasma concentration of Paclitaxel, DOTAP, Enlonstobart	3years
Phase Ib- ADA	Anti-Drug Antibodies	3years
Phase Ib- Nab	Neutralizing Anti-Drug Antibodies	3years
Phase II- PFS	Progression-Free Survival	3years
Phase II- DCR	Disease Control Rate	3years
Phase II- DoR	Duration of Response	3years
Phase II- TTR	Time to Response	3years
Phase II-ORR	Overall Response Rate	3years
Phase II- OS	Overall Survival	3years
Phase II- TEAE	Treatment-Emergent Adverse Event	3years
Phase II- SAE	Serious Adverse Event	3years
Phase II-PK：plasma concentration of Paclitaxel, DOTAP, Enlonstobart	Pharmacokinetics：plasma concentration of Paclitaxel, DOTAP, Enlonstobart	3years
Phase II- ADA	Anti-Drug Antibodies	3years
Phase II- Nab	Neutralizing Anti-Drug Antibodies	3years

Collaborators and Investigators

• Sponsor: CSPC ZhongQi Pharmaceutical Technology Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): December 23, 2025
• Primary Completion (Estimated): June 26, 2028
• Study Completion (Estimated): February 3, 2029

Study Registration Dates

• First Submitted: November 21, 2025
• First Submitted That Met QC Criteria: December 1, 2025
• First Posted (Actual): December 15, 2025

Study Record Updates

• Last Update Posted (Actual): December 15, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: pembrolizumab; lenvatinib
• Other Study ID Numbers: HA131-005

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No