Combination therapy of Cadonilimab and Lenvatinib for treating unresectable liver cancer

A Phase II, Single-arm, Multicenter, Prospective Study of Cadonilimab and Lenvatinib for Conversion Therapy in Unresectable Hepatocellular Carcinoma

This study is testing a combination of two drugs, Cadonilimab and Lenvatinib, to see if they can help people with liver cancer who can’t have surgery become eligible for surgery.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Peking Union Medical College Hospital (other)
• Drugs / interventions: radiation, prednisone, Cadonilimab, Enfortumab, Lenvatinib
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT06215651 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of Cadonilimab and Lenvatinib as a conversion therapy for patients with unresectable hepatocellular carcinoma (HCC). Participants will receive 3-4 cycles of the combination treatment, followed by imaging assessments to determine if they can proceed to surgical intervention. Those who do not successfully convert will either exit the study for alternative treatments or continue with the therapy if they do not show disease progression. The study aims to provide insights into the potential for surgical conversion in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with unresectable hepatocellular carcinoma and specific measurable lesions.

Not a fit: Patients with distant metastasis or those who have received prior systemic anticancer therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could enable surgical options for patients with previously unresectable liver cancer.

How similar studies have performed: While this approach is exploratory, similar combination therapies have shown promise in other studies, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Participants must sign a written informed consent form before enrollment. Age \>18 and ≤75 years, both genders are eligible. Patients with histologically or pathologically confirmed hepatocellular carcinoma (HCC) or meeting the clinical diagnostic criteria for HCC according to the American Association for the Study of Liver Diseases (AASLD).

BCLC stage C without distant or lymphatic metastasis, or BCLC stage B ineligible for curative surgical treatment.

Presence of measurable lesions (according to RECIST 1.1 criteria, CT scan long diameter ≥10 mm for non-lymph node lesions, CT scan short diameter ≥15 mm for lymph node lesions).

No prior systemic anticancer therapy. No prior local treatment for target lesions, including TAE, TACE, TARE, surgery, ablation, PEI, or radiotherapy.

Child-Pugh score \<7. ECOG PS score: 0-1. At least one untreated measurable lesion according to RECIST v1.1, or a measurable lesion with confirmed progression after local treatment (e.g., radiofrequency ablation, ethanol or acetic acid injection, cryoablation, high-intensity focused ultrasound, arterial embolization, arterial chemoembolization, etc.) per mRECIST criteria.

Expected survival \>12 weeks. Non-surgically sterilized or premenopausal female patients must use a medically approved contraceptive measure during the study treatment period and within 3 months after the end of the study treatment. Pregnancy tests for non-surgically sterilized premenopausal female patients must be negative within 7 days before study entry, and they must not be lactating. Non-surgically sterilized or fertile male patients must agree to use a medically approved contraceptive measure with their female partners during the study treatment period and within 3 months after the end of the study treatment.

Adequate organ function, excluding any blood component and growth factor use within 14 days:

Hematology: ANC ≥1.5×10\^9/L, PLT ≥50×10\^9/L, HGB ≥90g/L. Liver function: TBIL ≤3×ULN, ALT and AST ≤5×ULN, serum albumin ≥28 g/L, ALP ≤5×ULN, and must be stable for at least 1 week after routine liver protection treatment as assessed by the investigator.

Renal function: Cr ≤1.5×ULN or creatinine clearance ≥50 mL/min (using the standard Cockcroft-Gault formula), and urine protein \<2+; for patients with baseline urine protein ≥2+, a 24-hour urine collection and quantitative measurement with \<1g of protein is required.

Coagulation function: INR and APTT ≤1.5×ULN; for subjects receiving anticoagulant therapy, PT and INR should be within the planned range.

Exclusion Criteria:

* Previously histologically/cytologically confirmed hepatocellular carcinoma with fibrolamellar components, sarcomatoid hepatocellular carcinoma, cholangiocarcinoma, etc.

Prior local or systemic anti-tumor therapy. History of hepatic encephalopathy. History of liver transplantation. Clinically significant pericardial effusion requiring drainage or clinically symptomatic pleural effusion.

Clinically evident ascites defined as detectable on physical examination or requiring drainage during screening.

Concurrent HBV and HCV infection (HCV RNA negative patients with a history of HCV infection are considered uninfected).

Central nervous system metastasis or leptomeningeal metastasis. History of esophageal or gastric variceal bleeding due to portal hypertension in the first 6 months before the initial dose. Participants must have undergone esophagogastroduodenoscopy within 6 months before the first dose; participants with severe (Grade 3) varices are not allowed to participate in the study.

Patients with any bleeding diathesis signs or history, experiencing any bleeding or hemorrhagic events ≥CTCAE Grade 3 within the first 4 weeks before the initial dose.

Occurrence of arterial or venous thromboembolic events in the first 6 months before the initial dose, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis, or any severe history of thromboembolism. Exclusion criteria do not apply to stable thrombosis after routine anticoagulation therapy for implanted venous infusion ports or catheter-related thrombosis.

Uncontrolled hypertension, with systolic blood pressure \>150 mmHg or diastolic blood pressure \>90 mmHg after optimal medical treatment, hypertensive crisis, or a history of hypertensive encephalopathy.

Symptomatic congestive heart failure (New York Heart Association Class II-IV) or echocardiographic left ventricular ejection fraction (EF) \<50%. Symptomatic or poorly controlled arrhythmias, including atrial fibrillation or flutter with a ventricular rate \>100 beats/min, a history of congenital long QT syndrome, or a corrected QT interval (QTc) \>450 ms (male) or QTc \>470 ms (female) on screening (using the Fridericia method). A history of myocarditis, cardiomyopathy, or malignant arrhythmias.

Severe bleeding tendency or coagulation disorders, or receiving thrombolytic therapy. Currently using or recently used (within 10 days before the first dose of study treatment) aspirin (\>325 mg/day) or anticoagulants requiring INR monitoring (such as warfarin).

History of gastrointestinal perforation and/or fistula within the first 6 months before the initial dose, history of bowel obstruction (including incomplete bowel obstruction requiring parenteral nutrition), extensive colon resection (partial colon resection or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea.

Received radiation therapy within the first 3 weeks before the initial dose. Patients who received radiation therapy more than 7 days before the first dose can be enrolled. Presence of interstitial lung disease or interstitial lung disease requiring steroid treatment, either past or current.

Active pulmonary tuberculosis (TB), receiving anti-TB treatment, or having received anti-TB treatment within the past 1 year before the initial dose.

Subjects with any active autoimmune disease or a history of autoimmune disease (including but not limited to autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, and those who have undergone thyroid surgery cannot be included). Subjects with resolved childhood asthma without the need for intervention can be included; subjects with asthma requiring bronchodilators for medical intervention cannot be included.

Subjects using immunosuppressive agents, either systemic or locally absorbable steroids for immunosuppressive purposes (dose \>10 mg/day prednisone or equivalent), and still continuing within the last 2 weeks before enrollment.

Subjects with active infection or unexplained fever \>38.5°C during screening or within the first 4 weeks before the initial dose (subjects with fever related to tumor-induced fever can be included according to the investigator's judgment).

Patients with objective evidence of past or present lung fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, or severe impairment of lung function.

Subjects with congenital or acquired immunodeficiency, such as HIV infection. Subjects who have not received live vaccines within 4 weeks before the study medication or may receive live vaccines during the study period.

Subjects with a known history of substance abuse, alcohol abuse, or drug abuse. Patients unable to take oral medication. The investigator deems it necessary to exclude subjects from this study. For instance, based on the investigator's judgment, if a participant has other factors that could potentially lead to the premature termination of the study, such as the presence of other serious illnesses (including mental disorders) requiring concurrent treatment, severe gastroesophageal varices, significant laboratory abnormalities, or factors related to family or social circumstances that could impact the safety of the participant or the collection of data and samples.

Where this trial is running

Beijing, Beijing Municipality

• Hai-Tao Zhao — Beijing, Beijing Municipality, China (RECRUITING)

Conditions: Cadonilimab and Lenvatinib