Advanced Hepatocellular Carcinoma (HCC)Phase 1/2NCT07282509
Safety and Efficacy of Paclitaxel Liposome Arterial Infusion Combined With Systemic Therapy for Second-Line Treatment of Advanced Liver Cancer
A Phase 1/2 study testing HA131, Enlonstobart Injection and Pembrolizumab Injection in people with Advanced Hepatocellular Carcinoma (HCC), run by CSPC ZhongQi Pharmaceutical Technology Co., Ltd..
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Hepatocellular Carcinoma (HCC)
- What is being tested?
- HA131, Enlonstobart Injection and Pembrolizumab Injection
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 116 participants
- Where
- No sites listed yet
- Study dates
- 23 Dec 2025to 3 Feb 2029
- Phase
- Phase 1/2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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);
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- 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.
Who cannot join
- 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);
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- 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:
- 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);
- High-grade atrioventricular block;
- Malignant arrhythmia poorly controlled by medication;
- History of chronic heart failure with NYHA (New York Heart Association) functional class ≥ 3;
- Severe valvular heart regurgitation or stenosis requiring treatment;
- 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;
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: 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.
- Conditions
- Advanced Hepatocellular Carcinoma (HCC)
- Being tested
- HA131, Enlonstobart Injection, Pembrolizumab Injection, Lenvatinib Mesilate Capsules
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HA131Drug
Phase Ib: Dose escalation. Phase II: Administration at the RP2D dose determined in Phase Ib. Transcatheter Arterial Infusion.
Enlonstobart InjectionDrug
Administered via intravenous infusion.
Pembrolizumab InjectionDrug
Administered via intravenous infusion.
Lenvatinib Mesilate CapsulesDrug
Administered orally.
| Study group | Role | What they receive |
|---|---|---|
| Phase Ib Cohort 1 | Experimental | Lenvatinib combined with elonstobart. Receives: Drug: Enlonstobart Injection; Drug: Lenvatinib Mesilate Capsules |
| Phase Ib Cohort 2 | Experimental | Transcatheter arterial infusion of HA131 combined with systemic therapy (lenvatinib with pembrolizumab). Receives: 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 ) Receives: 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 ). Receives: Drug: HA131; Drug: Enlonstobart Injection; Drug: Lenvatinib Mesilate Capsules |
| Phase II Control Arm | Active comparator | Systemic therapy alone (lenvatinib with or without elonstobart ). Receives: Drug: Enlonstobart Injection; Drug: Lenvatinib Mesilate Capsules |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase Ib-DLT
Incidence of Dose-Limiting Toxicity
Measured: 3years
Phase Ib- AE
Adverse Event
Measured: 3years
Phase II- ORR
Overall Response Rate
Measured: 3years
Secondary outcomes (20)
Phase Ib- ORR
Overall Response Rate
Measured: 3years
Phase Ib- DCR
Disease Control Rate
Measured: 3years
Phase Ib- DoR
Duration of Response
Measured: 3years
Phase Ib- TTR
Time to Response
Measured: 3years
Phase Ib-PFS
Progression-Free Survival
Measured: 3years
Phase Ib- OS
Overall Survival
Measured: 3years
Phase Ib-PK：plasma concentration of Paclitaxel, DOTAP, Enlonstobart
Pharmacokinetics：plasma concentration of Paclitaxel, DOTAP, Enlonstobart
Measured: 3years
Phase Ib- ADA
Anti-Drug Antibodies
Measured: 3years
Phase Ib- Nab
Neutralizing Anti-Drug Antibodies
Measured: 3years
Phase II- PFS
Progression-Free Survival
Measured: 3years
Phase II- DCR
Disease Control Rate
Measured: 3years
Phase II- DoR
Duration of Response
Measured: 3years
Phase II- TTR
Time to Response
Measured: 3years
Phase II-ORR
Overall Response Rate
Measured: 3years
Phase II- OS
Overall Survival
Measured: 3years
Phase II- TEAE
Treatment-Emergent Adverse Event
Measured: 3years
Phase II- SAE
Serious Adverse Event
Measured: 3years
Phase II-PK：plasma concentration of Paclitaxel, DOTAP, Enlonstobart
Pharmacokinetics：plasma concentration of Paclitaxel, DOTAP, Enlonstobart
Measured: 3years
Phase II- ADA
Anti-Drug Antibodies
Measured: 3years
Phase II- Nab
Neutralizing Anti-Drug Antibodies
Measured: 3years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2025
- Study start23 Dec 2025 (estimated)
- Primary completion26 Jun 2028 (estimated)
- Study completion3 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Hepatocellular Carcinoma (HCC)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 116 participants (estimated)
Sponsor and investigators
- Lead sponsor
- CSPC ZhongQi Pharmaceutical Technology Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07282509
- Sponsor's protocol ID
- HA131-005
- Status last verified
- Dec 2025
- First submitted
- 21 Nov 2025
- Last updated
- 15 Dec 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No