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Hepatocellular Carcinoma (HCC)Phase 2DRIVE-IINCT07138885

A Phase II, Single-Arm, Prospective Trial on the Efficacy and Safety of QL1706 Combination Regimen as Second-Line Therapy for Targeted-Immunotherapy-Resistant Hepatocellular Carcinoma

A Phase 2 study testing HAI-FOLFOX + bevacizumab + QL1706 and TACE + bevacizumab + TAS-102 + QL1706 in people with Hepatocellular Carcinoma (HCC) and Second Line Treatment, run by Sun Yat-sen University at 1 site in China.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The goal of this prospective Phase II clinical trial is to evaluate the efficacy and safety of QL1706-based combination therapy in patients with hepatocellular carcinoma (HCC) who have failed prior targeted-immunotherapy (e.g., anti-PD-1/PD-L1 + antiangiogenic therapy). Read more about this study

Who is it for?
Ages 18 to 65 days
What is being tested?
HAI-FOLFOX + bevacizumab + QL1706 and TACE + bevacizumab + TAS-102 + QL1706
Could I receive a placebo?
No, everyone receives an active treatment
How many people
62 participants
Where
1 siteChina
Study dates
1 Aug 2025to 31 Jul 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

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 65 days
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Voluntary Participation, Willingly signs the written informed consent form.
  • Aged 18-65 years (inclusive), any gender.
  • Histologically, cytologically, or clinically confirmed hepatocellular carcinoma (HCC) with disease progression after first-line targeted therapy combined with immunotherapy, or intolerable to first-line targeted-immunotherapy combination treatment.
  • No prior exposure to VEGF monoclonal antibodies, CTLA-4 inhibitors, or bispecific antibodies. For arm 1: No prior treatment with oxaliplatin or fluorouracil-based drugs.
  • Liver Function: Child-Pugh class A or class B (score ≤7), with no history of hepatic encephalopathy.
  • Performance Status: ECOG PS score 0 or 1.
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  • Life Expectancy ≥12 weeks.
  • Measurable Lesion: ≥1 measurable target lesion per RECIST v1.1 (not previously irradiated/localized; lesions in prior treatment areas are acceptable if progression is confirmed).
  • Preserved organ \& bone marrow function (within 7 days before treatment; no blood products/growth factors within 14 days prior):
  • Neutrophil count (ANC) ≥1.5×10⁹/L
  • Platelets ≥75×10⁹/L
  • Hemoglobin ≥90 g/L
  • Albumin ≥28 g/L
  • ALT/AST/Alkaline phosphatase (AKP) ≤3×ULN
  • Total bilirubin (TBIL) ≤2×ULN
  • INR ≤2 or PT prolongation ≤6 sec above ULN
  • Urine protein <2+ (if ≥2+, 24-hour urine protein must be <1.0 g).
  • Viral Hepatitis Management
  • If HBsAg-positive: HBV DNA <2000 IU/mL or 10⁴ copies/mL, with ongoing antiviral therapy (entecavir/tenofovir disoproxil fumarate/tenofovir alafenamide/emtecavir).
  • HCV-infected patients with undetectable HCV RNA are considered HCV-negative.
  • Contraception
  • Fertile participants (male/female) must use reliable contraception (hormonal/barrier/abstinence) during and for ≥180 days post-treatment.
  • Women of childbearing potential must have a negative serum pregnancy test within 7 days before enrollment.

Who cannot join

  • Histologically/cytologically confirmed fibrolamellar HCC, sarcomatoid HCC, cholangiocarcinoma, or mixed hepatocellular-cholangiocarcinoma.
  • Other active malignancies within 5 years prior to enrollment, except cured localized tumors (e.g., basal cell carcinoma, squamous cell skin cancer, superficial bladder cancer, in situ prostate/cervical/breast cancer).
  • History of or planned liver transplantation.
  • Clinically significant ascites requiring therapeutic paracentesis, uncontrolled pleural/pericardial effusion (asymptomatic minimal ascites on imaging allowed).
  • Known CNS metastases or leptomeningeal disease.
  • Tumor thrombus involving both main portal vein and superior mesenteric vein, or portal vein and inferior vena cava.
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  • High-risk variceal bleeding:
  • Esophageal/gastric variceal bleeding within 6 months
  • High-grade varices on endoscopy within 3 months
  • Portal hypertension with bleeding risk (splenomegaly, active ulcers, occult blood+, or endoscopic "red signs").
  • Life-threatening hemorrhage within 3 months requiring transfusion/surgery/medical intervention.
  • Significant bleeding risk:
  • Hemoptysis/tumor bleeding within 2 weeks
  • Thromboembolism within 6 months
  • Therapeutic anticoagulation (except prophylactic LMWH) within 2 weeks
  • Antiplatelet therapy (aspirin >325 mg/day, clopidogrel >75 mg/day) within 10 days
  • Tumor invasion of major vessels/airways/mediastinum.
  • Severe cardiovascular disease:
  • Significant arrhythmias (requiring intervention), QTcF ≥450 ms (M)/470 ms (F)
  • ACS/heart failure/stroke/TIA within 6 months
  • NYHA class ≥II or LVEF <50%
  • Uncontrolled hypertension (≥160/100 mmHg despite ≥2 agents).
  • Abdominal fistula/GI perforation/abscess within 6 months.
  • Bowel obstruction/clinical signs of GI obstruction within 6 months.
  • Non-healing wounds, active ulcers, or untreated fractures.
  • Active autoimmune diseases or history of autoimmune diseases with potential recurrence (including but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism [patients with hypothyroidism controlled by hormone replacement therapy alone are not excluded]). Note: Patients with non-systemic skin conditions (e.g., vitiligo, psoriasis, alopecia), well-controlled type 1 diabetes on insulin, or childhood asthma with complete remission in adulthood requiring no intervention may be enrolled. Asthma patients requiring bronchodilator therapy are excluded.
  • Immunosuppressants (>10 mg/day prednisone equivalent) within 2 weeks.
  • Severe hypersensitivity to monoclonal antibodies.
  • Hepatic encephalopathy or CNS metastases.
  • Organ transplant history.
  • Symptomatic ascites requiring drainage within 3 months.
  • Uncontrolled hypertension (≥140/90 mmHg despite treatment).
  • Arterial/venous thrombosis within 6 months (stroke, DVT, PE).
  • Bleeding/thrombotic disorders (hemophilia, coagulopathy, thrombocytopenia).
  • Proteinuria ≥++ with 24-h urine protein >1.0 g.
  • Active infection (fever ≥38.5°C within 7 days or WBC >15×10⁹/L).
  • Interstitial lung disease (current or steroid-requiring history).
  • Active tuberculosis (confirmed by imaging/sputum/clinical assessment).
  • Immunodeficiency (HIV/syphilis).
  • Severe infection within 4 weeks (hospitalization required) or antibiotics within 2 weeks (prophylaxis allowed).
  • Recent treatments:
  • Liver surgery/HCC locoregional therapy within 4 weeks
  • Palliative bone radiotherapy within 2 weeks
  • Anti-HCC herbal medicine within 2 weeks
  • Unresolved toxicities (>Grade 1 per CTCAE v5.0, except alopecia).
  • Immunomodulators (interferons, interleukins) within 2 weeks.
  • Other investigational drugs within 4 weeks.
  • Allogeneic stem cell/organ transplant.
  • HBV-HCV coinfection.
  • Hypersensitivity to trial drug components/monoclonal antibodies/antiangiogenic agents.
  • Live vaccines within 4 weeks or planned during study.
  • Major surgery within 4 weeks or planned during study (biopsies/IV catheterization allowed).
  • Other exclusionary factors per investigator judgment (substance abuse, severe comorbidities, psychosocial risks).

Trial locations and contacts

1 site in 1 country.

China1 site

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong, 510060

Other trials in China

About this study

The goal of this prospective Phase II clinical trial is to evaluate the efficacy and safety of QL1706-based combination therapy in patients with hepatocellular carcinoma (HCC) who have failed prior targeted-immunotherapy (e.g., anti-PD-1/PD-L1 + antiangiogenic therapy).

The main question is:

Read more

Can the combination of localized-regional therapy (e.g., HAIC/TACE) and systemic dual immunotherapy (QL1706) overcome resistance and improve outcomes in second-line HCC treatment?

Participants will:

  1. Receive QL1706 (a dual immune checkpoint inhibitor) combined with either: Hepatic arterial infusion chemotherapy (HAIC)/transarterial chemoembolization (TACE), or Antiangiogenic targeted therapy.
  2. Undergo regular imaging (e.g., MRI/CT) and biomarker assessments for efficacy monitoring.
  3. Be evaluated for adverse events (AEs) and quality of life.

This study seeks to establish a novel therapeutic paradigm for HCC patients after targeted-immunotherapy failure, addressing the unmet need for evidence-based second-line strategies.

Being tested
HAI-FOLFOX + bevacizumab + QL1706, TACE + bevacizumab + TAS-102 + QL1706
Keywords
Second line treatment, Hepatocellular Carcinoma (HCC), Immunotherapy resistance
Medical subject headings
Carcinoma, Hepatocellular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HAI-FOLFOX + bevacizumab + QL1706Procedure or surgery

    Also called HAI-FOLFOX, bevacizumab, QL1706

    Arm 1:

    HAI-FOLFOX Administration (Day 1 of Each Cycle) Super-selective insertion the arterial catheter into the tumor-feeding artery, then infusion: Oxaliplatin: 85 mg/m², Leucovorin: 400 mg/m², 5-FU: 2500 mg/m²

    Administer bevacizumab (7.5 mg/kg; total dose capped at 300 mg or 400 mg) via arterial infusion.

    Then QL1706 (5 mg/kg, IV infusion, Q3W).

    Treatment Schedule: Repeat HAI-FOLFOX + arterial bevacizumab every 3 weeks (max 6 cycles), followed by QL1706 maintenance (Q3W).

  • TACE + bevacizumab + TAS-102 + QL1706Procedure or surgery

    Also called bevacizumab, TAS-102, QL1706, TACE

    Arm 2:

    On-Demand TACE (Lipiodol: ≤10 mL, mixed with platinum + doxorubicin agent, each ≤50 mg) to form an emulsion. Repeat TACE until TACE resistance develops (typically ~4 sessions).

    Administer bevacizumab (7.5 mg/kg; total dose capped at 300 mg or 400 mg) via intra-arterial route.

    After first TACE, begin TAS-102 (15 mg/m² po BID) once liver function recovers to acceptable levels.

    Then QL1706 (5 mg/kg, IV infusion, Q3W).

Study groups in NCT07138885
Study groupRoleWhat they receive
HAI-FOLFOX + bevacizumab + QL1706ExperimentalTo evaluate the objective response rate (ORR) of HAI-FOLFOX + bevacizumab + QL1706 in patients with intermediate-advanced hepatocellular carcinoma (HCC) who developed resistance or recurrence after prior treatment with surgical resection/ablation/TACE combined with TKIs and/or PD-(L)1 inhibitors.
Receives: Procedure: HAI-FOLFOX + bevacizumab + QL1706
TACE + bevacizumab + QL1706 + TAS-102ExperimentalTo evaluate the objective response rate (ORR) of TACE + bevacizumab + TAS-102 + QL1706 in patients with intermediate-advanced HCC who developed resistance or recurrence after prior HAI-FOLFOX combined with TKIs and/or PD-(L)1 inhibitors.
Receives: Procedure: TACE + bevacizumab + TAS-102 + QL1706

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Objective response rate (ORR) by RECIST 1.1

    ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by RECIST 1.1.

    Measured: From date of first dose of study drug until disease progression (up to approximately 3 years)

Secondary outcomes (10)

  1. Objective response rate (ORR) by mRECIST

    ORR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) at the time of data cutoff as assessed by mRECIST.

    Measured: From date of first dose of study drug until disease progression (up to approximately 3 years)

  2. The disease control rate (DCR)

    DCR is defined as the percentage of participants who have best overall response (BOR) of complete response (CR) or partial response (PR) or stable disease (SD) at the time of data cutoff as assessed by RECIST 1.1 and mRECIST.

    Measured: From date of first dose of study drug until disease progression, stable disease (up to approximately 3 years)

  3. The time to response (TTR)

    TTR was calculated as the time from treatment initiation to first documented response as assessed by RECIST 1.1 and mRECIST.

    Measured: From date of first dose of study drug to the date of first documentation of CR or PR (up to approximately 3 years)

  4. Duration of response (DOR) by RECIST 1.1 and mRECIST

    DOR is defined as the time from the first documentation of CR or PR to the date of first documentation of disease progression as assessed by RECIST 1.1 and mRECIST or death (whichever occurs first).

    Measured: From the first documentation of CR or PR to the first date of documentation of disease progression or death whichever occurs first (up to approximately 3 years)

  5. The progression-free survival time (PFS)

    The progression-free survival time (PFS) defined as the time from the first study dose date to the date of first documentation of disease progression as assessed by RECIST 1.1 and mRECIST or death, whichever comes earlier.

    Measured: From date of first dose of study drug to the date of first documentation of disease progression or death (up to approximately 3 years)

  6. The median overall survival time (OS)

    OS is measured from the start date of the Treatment Phase (date of first study dose) until date of death from any cause. Participants who are lost to follow-up and the participants who are alive at the date of data cutoff will be censored at the date the participant was last known alive or the cut-off date.

    Measured: From the start date of the Treatment Phase until date of death from any cause (up to approximately 3 years)

  7. The progression-free survival rate (PFSR) by RECIST 1.1 and mRECIST

    Measured: From date of first dose of study drug to the date of first documentation of disease progression or death, whichever occurs first (up to approximately 3 years)

  8. The overall survival rate (OSR)

    Measured: From date of first dose of study drug to the date of documentation of death from any cause (up to approximately 3 years)

  9. Number of participants with treatment-related adverse events as assessed by CTCAE v5.0

    Measured: From the start date of the Treatment Phase until date of death from any cause (up to approximately 3 years)

  10. Exploratory outcome measure: The quality of life (QoL)

    The exploratory endpoint was the QoL, which was assessed using the European Organisation for Research and Treatment of Cancer QoL questionnaire (EORTC QLQ-C30).

    Measured: From date of first dose of study drug to the date of first documentation of disease progression within the liver or death (up to approximately 3 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Aug 2025
  2. Study start1 Aug 2025
  3. Primary completion31 Jul 2027 (estimated)
  4. Study completion31 Jul 2028 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
Arm 1: To evaluate the objective response rate (ORR) of HAI-FOLFOX + bevacizumab + QL1706 (iparomlimab and tuvonralimab, PD-1/CTLA-4 dual inhibitor) in patients with intermediate-advanced hepatocellular carcinoma (HCC) who developed resistance or recurrence after prior treatment with surgical resection/ablation/TACE combined with TKIs and/or PD-(L)1 inhibitors. Arm 2: To evaluate the objective response rate (ORR) of TACE + bevacizumab + TAS-102 + QL1706 in patients with intermediate-advanced HCC who developed resistance or recurrence after prior HAI-FOLFOX combined with TKIs and/or PD-(L)1 inhibitors.
Masking
None (open label)
Enrolment
62 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07138885
Sponsor's protocol ID
DRIVE-II
Acronym
DRIVE-II
Status last verified
Apr 2026
First submitted
17 Aug 2025
Last updated
29 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Study Protocol, Statistical Analysis Plan (SAP), and Clinical Study Report (CSR)

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing HAI-FOLFOX + bevacizumab + QL1706 and TACE + bevacizumab + TAS-102 + QL1706 in people with Hepatocellular Carcinoma (HCC) and Second Line Treatment, run by Sun Yat-sen University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 53 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) by RECIST 1.1 (time frame: From date of first dose of study drug until disease progression (up to approximately 3 years)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07138885.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2026.

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