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

NCT07282509 | Not Yet Recruiting Phase 1

• 1 other identifier: HA131-005
• Study Type: interventional
• Target: 116
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Advanced Hepatocellular Carcinoma (HCC)

Outcome Measures

Primary Outcomes (3)

• Phase Ib-DLT

  Incidence of Dose-Limiting Toxicity

  3years

• Phase Ib- AE

  Adverse Event

  3years

• Phase II- ORR

  Overall Response Rate

  3years

Secondary Outcomes (20)

• Phase Ib- ORR

  3years

• Phase Ib- DCR

  3years

• Phase Ib- DoR

  3years

• Phase Ib- TTR

  3years

• Phase Ib-PFS

  3years

Study Arms (5)

Phase Ib Cohort 1

EXPERIMENTAL

Lenvatinib combined with elonstobart.

Drug: Enlonstobart Injection; Drug: Lenvatinib Mesilate Capsules

Phase Ib Cohort 2

EXPERIMENTAL

Transcatheter arterial infusion of HA131 combined with systemic therapy (lenvatinib with pembrolizumab).

Drug: HA131; Drug: Pembrolizumab Injection; Drug: Lenvatinib Mesilate Capsules

Phase Ib Cohort 3

EXPERIMENTAL

Transcatheter arterial infusion of HA131 combined with systemic therapy (lenvatinib with elonstobart )

Drug: HA131; Drug: Enlonstobart Injection; Drug: Lenvatinib Mesilate Capsules

Phase II Experimental Arm

EXPERIMENTAL

Transcatheter arterial infusion of HA131 combined with systemic therapy (lenvatinib with or without elonstobart ).

Drug: HA131; Drug: Enlonstobart Injection; Drug: Lenvatinib Mesilate Capsules

Phase II Control Arm

ACTIVE COMPARATOR

Systemic therapy alone (lenvatinib with or without elonstobart ).

Drug: Enlonstobart Injection; Drug: Lenvatinib Mesilate Capsules

Interventions

HA131 DRUG

Phase Ib: Dose escalation. Phase II: Administration at the RP2D dose determined in Phase Ib. Transcatheter Arterial Infusion.

Phase II Experimental Arm; Phase Ib Cohort 2; Phase Ib Cohort 3

Enlonstobart Injection DRUG

Administered via intravenous infusion.

Phase II Control Arm; Phase II Experimental Arm; Phase Ib Cohort 1; Phase Ib Cohort 3

Pembrolizumab Injection DRUG

Administered via intravenous infusion.

Phase Ib Cohort 2

Lenvatinib Mesilate Capsules DRUG

Administered orally.

Phase II Control Arm; Phase II Experimental Arm; Phase Ib Cohort 1; Phase Ib Cohort 2; Phase Ib Cohort 3

Eligibility Criteria

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

You may qualify if:

• Aged 18 to 75 years (inclusive), regardless of gender;
• Diagnosed with hepatocellular carcinoma (HCC) by histopathology, cytology, or imaging;
• 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);
• Child-Pugh liver function class ≤ 7 points within 7 days prior to the first dose administration;
• Progressive disease after prior first-line systemic antineoplastic therapy containing PD-1/PD-L1 monoclonal antibody;
• 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);
• ECOG (Eastern Cooperative Oncology Group) Performance Status (PS) score: 0-1.
• Controlled hypertension, with blood pressure ≤ 150/90 mmHg and no changes to the antihypertensive regimen within one week prior to screening;
• Estimated survival time of more than 3 months;
• Before randomization, major organ/system functions are basically normal, meeting the criteria as assessed by laboratory tests.
• 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;
• Participants must be informed about the study prior to the trial and voluntarily sign a written informed consent form.

You may not qualify if:

• Pathologically confirmed fibrolamellar hepatocellular carcinoma (HCC), sarcomatoid HCC, cholangiocellular carcinoma, or combined hepatocellular-cholangiocarcinoma;
• History of liver surgery and/or local treatment for HCC within 4 weeks prior to the first dose;
• Previous antineoplastic treatment with lenvatinib;
• 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.
• Active brain metastases, leptomeningeal disease, or uncontrolled spinal cord compression;
• 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);
• 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;
• Malabsorption syndrome or inability to take oral medications due to other reasons;
• 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;
• 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);
• History of autoimmune disease, immunodeficiency, other acquired or congenital immunodeficiency diseases, or current use of immunosuppressants;
• Untreated active hepatitis B.
• 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;
• Participants with active syphilis;
• A history of past or current hepatic encephalopathy;

Sponsors & Collaborators

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

MeSH Terms

Interventions

pembrolizumab; lenvatinib

Central Study Contacts

Clinical Trials Information Group officer

CONTACT

86-0311-69085587; ctr-contact@cspc.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 15, 2025
• Study Start: December 23, 2025
• Primary Completion (Estimated): June 26, 2028
• Study Completion (Estimated): February 3, 2029
• Last Updated: December 15, 2025

Record last verified: 2025-12