Pre-surgery treatment with iparomlimab, tuvonralimab, and lenvatinib for liver cancer
An Exploratory Study on the Neoadjuvant Therapy of iIparomlimab and Tuvonralimab Combined With Lenvatinib for Hepatocellular Carcinoma
This trial will try a 9-week pre-surgery combination of two immune antibodies (iparomlimab and tuvonralimab) plus daily lenvatinib in people with resectable hepatocellular carcinoma who are at high risk of recurrence.
Quick facts
| Phase | Phase 2 |
|---|---|
| Study type | Interventional |
| Enrollment | 33 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Peking Union Medical College Hospital Academic / other |
| Drugs / interventions | radiation, iIparomlimab, Tuvonralimab, lenvatinib, ofIparomlimab, Iparomlimab |
| Locations | 1 site (Beijing, Beijing Municipality) |
| Trial ID | NCT07014150 on ClinicalTrials.gov |
What this trial studies
This is a single-center, single-arm, open-label Phase 2 trial enrolling 30 patients with resectable hepatocellular carcinoma and predefined high-risk features for postoperative recurrence. Participants receive iparomlimab and tuvonralimab intravenously every three weeks for three cycles alongside daily oral lenvatinib for nine weeks before planned surgery. The primary endpoint is major pathological response in the resected tumor, with secondary endpoints including pathological complete response, progression-free survival, overall survival, recurrence-free survival, and objective response and disease control rates, plus standard safety monitoring. An exploratory objective examines changes in the tumor immune microenvironment in tissue and blood samples.
Who should consider this trial
Good fit: Adults (≥18 years) with resectable HCC (CNLC Ib–IIIa), at least one high-risk feature for recurrence (for example AFP >400 ng/mL, single tumor >5 cm, >3 tumors or any >3 cm, vascular invasion or tumor adjacent to major vessels), ECOG 0–1, measurable disease per RECIST 1.1, and no prior systemic therapy are ideal candidates.
Not a fit: Patients with unresectable or metastatic HCC, prior systemic treatment, poor performance status, significant organ dysfunction, or non-HCC liver tumors are unlikely to benefit from this neoadjuvant regimen.
Why it matters
Potential benefit: If successful, the regimen could lower the chance of cancer coming back after surgery and improve pathological tumor responses before resection.
How similar studies have performed: Other trials combining immune checkpoint inhibitors with tyrosine kinase inhibitors (for example PD-1 inhibitors plus lenvatinib) in HCC have shown promising tumor responses, but durable survival benefits and broader validation remain under study.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * The subjects voluntarily participated in the study and agreed to sign the written informed consent. They had good compliance and cooperated with the follow-up * Be at least 18 years old at the time of signing the informed consent form, with no gender restrictions. * Hepatocellular carcinoma diagnosed by histology or imaging * At least one measurable lesion (according to the requirements of RECIST version 1.1, the long diameter of the measurable lesion on spiral CT scan is ≥10mm or the short diameter of the enlarged lymph node is ≥15mm) * No systematic treatment has been received before * CNLC：Ib to IIIa * There is at least one of the following high-risk factors for postoperative recurrence: AFP\>400ng/ml; Single tumor \>5cm; The number of tumors is greater than 3 or any one of them is greater than 3cm; There are vascular tumor thrombus or tumors adjacent to large blood vessels, etc. * The ECOG score was 0-1 within one week before enrollment * Hematology and organ functions are adequate * Fertile women: Agree to abstain from sex (avoid heterosexual intercourse) or use contraceptive methods with an annual contraceptive failure rate of less than 1% during the treatment period and for at least 6 months after the last administration Exclusion Criteria: * Have received any systemic treatment * ECOG score \>1 * Definite extrahepatic metastasis * Pregnant women (with a positive pregnancy test before taking the medicine) or lactating women * Those who are known to be allergic or intolerant to recombinant humanized PD-1 monoclonal antibody drugs and their components (or any excipients) * Previous or existing grade 3 or above digestive tract fistulas or non-digestive tract fistulas (such as skin) as defined by CTCAE 5.0 criteria * Major surgical operations (except biopsy) have been performed within 4 weeks before the first study of drug treatment or the surgical incision has not fully healed * Cardiovascular and cerebrovascular diseases with significant clinical significance, including but not limited to acute myocardial infarction and severe/unstable angina pectoris that occurred within 6 months before enrollment * Insufficiency of liver and kidney functions, such as jaundice, ascites, and/or bilirubin \>3×ULN, creatinine ratio \>3.5g/24 hours, etc * Persistent infection of grade \>2 (CTCAE 5.0) * A history of thromboembolism (including stroke and/or transient ischemic attack) within the past 6 months * Hypertension that has not been well controlled after antihypertensive drug treatment (systolic blood pressure \>160mmHg, diastolic blood pressure \>100mmHg) * An active autoimmune disease or a history of autoimmune diseases in the past two years * Active central nervous system (CNS) metastases and/or cancerous meningitis * Be ready or have received organ or allogeneic bone marrow transplants before * Known history of active tuberculosis (Mycobacterium tuberculosis) * A history of gastrointestinal bleeding within the past 6 months or a clear tendency towards gastrointestinal bleeding * History of human immunodeficiency virus (HIV) infection * Positive for active hepatitis B or hepatitis C and has not received regular treatment. During the screening period, HBV DNA≥2000 IU/ml (or ≥104 copy number /ml), entecavir must be used to reduce it to \<2000 IU/ml (or \< 104 copy number /ml) before enrollment * There is drug abuse; Or any medical, psychological or social conditions that may affect the research, cause unstable patient compliance, or even endanger patient safety * Unresolved toxicity of grade \> 1 due to any previous treatment/procedure (CTCAE 5.0, excluding alopecia, anemia, and hypothyroidism). * Patients with objective evidence of severe lung function impairment in the past or at present, such as a history of severe pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonitis, and drug-related pneumonia * Received treatment with potent CYP3A4 inhibitors within 7 days before participating in the study * Accompanied by other malignant tumors, but having had other untreated malignant tumors in the past (within 5 years) or simultaneously, for cured basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the breast and carcinoma in situ of the cervix, treated superficial bladder cancer and prostate adenocarcinoma that has undergone surgical treatment and whose PSA tumor markers are within the normal range. * After a comprehensive assessment of the patient's condition by the researchers, it was determined that they were not suitable to participate in this research * Participate in another clinical study
Where this trial is running
Beijing, Beijing Municipality
- Chinese Academy of Medical Sciences，Peking Union Medical College Hospital — Beijing, Beijing Municipality, China (Recruiting)
Study contacts
- Study coordinator: Chengjie Li
- Email: 1624271942@qq.com
- Phone: 86+13733879582
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.