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Cadonilimab and LenvatinibPhase 2NCT06215651

Cadonilimab and Lenvatinib for Conversion Therapy in Unresectable Hepatocellular Carcinoma

A Phase 2 study testing Cadonilimab lenvatinib in people with Cadonilimab and Lenvatinib, run by Peking Union Medical College Hospital at 1 site in China.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

This study is a single-arm, open-label, exploratory clinical trial designed to assess the effectiveness and safety of the combination therapy of Cadonilimab and Lenvatinib for conversion treatment in unresectable hepatocellular carcinoma. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Cadonilimab and Lenvatinib
What is being tested?
Cadonilimab lenvatinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteChina
Study dates
11 Mar 2024to Jan 2027
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 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

China1 site, 1 recruiting

  • Hai-Tao Zhao

    Beijing, Beijing Municipality, 100730

    Hai-Tao Zhao, M.D., 01069156042, zhaoht@pumch.cn

    Recruiting

Other trials in China

About this study

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

This study is a single-arm, open-label, exploratory clinical trial designed to assess the effectiveness and safety of the combination therapy of Cadonilimab and Lenvatinib for conversion treatment in unresectable hepatocellular carcinoma. Eligible patients, meeting the inclusion criteria and providing informed consent, will undergo 3-4 cycles of Cadonilimab and Lenvatinib conversion therapy. A single imaging assessment will be conducted, and successfully converted patients will proceed to surgical treatment, with pathological evaluation of intraoperative specimens. Post-surgery, patients will choose an appropriate adjuvant treatment based on prior treatment benefits, disease baseline, and personal preferences.

Patients who do not successfully convert and experience disease progression will exit the study for alternative treatment. Those who do not successfully convert but do not exhibit disease progression will continue conversion treatment with Cadonilimab and Lenvatinib±TACE/HAIC, with tumor imaging assessments every 3 cycles. Successfully converted patients will undergo surgery, followed by the selection of an appropriate adjuvant treatment based on prior treatment benefits, disease baseline, and personal preferences.

Patients who do not successfully convert and experience disease progression will exit the study for alternative treatment. Those who do not successfully convert but do not exhibit disease progression will continue conversion treatment with Cadonilimab and Lenvatinib±TACE/HAIC until disease progression or intolerable toxicity occurs, with a maximum treatment duration of 2 years. Efficacy assessment will use mRECIST and RECIST v1.1 criteria, and safety evaluation will follow CTCAE 5.0 standards. Adverse events will be recorded throughout the study, with a period extending to 60 days after treatment completion for serious adverse events or those related to Enfortumab Vedotin, and in some cases extended to 90 days post-treatment.

Being tested
Cadonilimab lenvatinib

What participants receive

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

  • Cadonilimab lenvatinibDrug

    Also called AK104

    ±TACE/HAIC

Study groups in NCT06215651
Study groupRoleWhat they receive
Cadonilimab and lenvatinibExperimentalthe combination therapy of Cadonilimab and Lenvatinib for conversion treatment in unresectable hepatocellular carcinoma
Receives: Drug: Cadonilimab lenvatinib

What is being measured

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

  1. Objective response rate

    The proportion of patients whose tumor volume shrinks to a predetermined value and can maintain the minimum required duration, including complete response and partial response.

    Measured: Baseline up to approximately 6 months

  2. Conversion success rate

    Successful conversion criteria are as follows

    • Child-Pugh score <7
    • ECOG PS 0 or 1
    • No extrahepatic lesions or complete necrosis of extrahepatic lesions
    • Preservation of the intact vascular architecture of the liver
    • Adequate FLR after resection (≥35%)

    Measured: Baseline up to approximately 6 months

Secondary outcomes (3)

  1. Disease control rate

    It refers to the proportion of patients whose tumor volume control (shrinkage or enlargement) reaches a predetermined value and can maintain the minimum required duration. According to the RECIST criteria (version 1.1), during the treatment period or within 30 days after the discontinuation of the investigational drug, it is the sum of the percentage of subjects who achieve complete response (CR), partial response (PR), and stable disease (SD).

    Measured: Baseline up to approximately 6 months

  2. Progression-free survival

    It refers to the time from the first administration of the regimen to the first occurrence of disease progression or death due to any cause in the subjects.

    Measured: Baseline up to approximately 12 months

  3. Overall survival

    The time from randomization to death due to any cause in the subjects.

    Measured: Baseline up to approximately 24 months

Timeline

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

  1. First posted22 Jan 2024
  2. Study start11 Mar 2024
  3. Primary completionJan 2025 (estimated)
  4. Study completionJan 2027 (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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06215651
Sponsor's protocol ID
K4948
Status last verified
Mar 2024
First submitted
10 Jan 2024
Last updated
1 Apr 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cadonilimab lenvatinib in people with Cadonilimab and Lenvatinib, run by Peking Union Medical College Hospital 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 10 inclusion and 19 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: looking for participants now, as of the sponsor's last update on 1 Apr 2024. 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?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (time frame: Baseline up to approximately 6 months). The study lists 2 primary outcomes in all. 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 NCT06215651.

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 1 Apr 2024.

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