Status:
ACTIVE_NOT_RECRUITING
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
Lead Sponsor:
Sun Yat-sen University
Collaborating Sponsors:
Qilu Pharmaceutical Co., Ltd.
Conditions:
Hepatocellular Carcinoma (HCC)
Second Line Treatment
Eligibility:
All Genders
18-65 years
Phase:
PHASE2
Brief 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 ta...
Eligibility Criteria
Inclusion
- 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.
- 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.
Exclusion
- 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.
- 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).
Key Trial Info
Start Date :
August 1 2025
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 31 2028
Estimated Enrollment :
62 Patients enrolled
Trial Details
Trial ID
NCT07138885
Start Date
August 1 2025
End Date
July 31 2028
Last Update
August 24 2025
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, China, 510060