A Prospective, Single-Arm, Exploratory Study of the Safety and Efficacy of Neoadjuvant Treatment With QL1706, an Anti-PD-1/Anti-CTLA-4 Bispecific Antibody, in Resectable Stage IB and IIA Hepatocellular Carcinoma With High Recurrence Risk

Official title

A Prospective, Single-Arm, Exploratory Study of the Safety and Efficacy of Neoadjuvant Treatment With Iparomlimab and Tuvonralimab Injection, an Anti-PD-1/Anti-CTLA-4 Bispecific Antibody, in Resectable Stage IB and IIA Hepatocellular Carcinoma With High Recurrence Risk

Overview

This study aims to investigate the efficacy and safety of neoadjuvant therapy with Iparomlimab and Tuvonralimab Injection (anti-PD-1 and anti-CTLA-4 antibody combination) in patients with resectable hepatocellular carcinoma at high risk of recurrence (Stage IB, Stage IIA).

Interventions

• Drug Iparomlimab and Tuvonralimab
  Patients in the neoadjuvant Iparomlimab and Tuvonralimab group received 2 cycles of 7.5 mg/kg iv d1 q3w, followed by elective surgery 2-3 weeks thereafter.

Primary outcome measures

• 1-year disease-free survival rate [Time frame: 2 years]

Secondary outcome measures (6)

• Incidence of microvascular invasion (MVI) [Time frame: 2 years]
• Pathological complete response (pCR) rate [Time frame: 2 years]
• Objective response rate (ORR) [Time frame: 2 years]
• 2-year disease-free survival (DFS) rate [Time frame: 3 years]
• Overall survival (OS) rate [Time frame: 5 years]
• AE [Time frame: 2 years]

Eligibility criteria

Inclusion criteria

• Patients voluntarily participate in this study and sign the informed consent form.
• Aged 18 to 75 years, male or female.
• ECOG Performance Status (PS) score of 0 to 1.
• Child-Pugh liver function classification: Grade A.
• Histopathologically confirmed primary hepatocellular carcinoma (HCC), and the lesions meet the surgical resection indications specified in the Guidelines for the Diagnosis and Treatment of Primary Liver Cancer (2022 Edition).
• Preoperatively, evaluated by the investigator, with high recurrence risk factors, meeting at least one of the following: Stage IB: Single tumor with maximum diameter > 5 cm; 2-3 tumors with maximum tumor diameter ≤ 3 cm；Stage IIA: 2-3 tumors with maximum tumor diameter > 3 cm.
• According to the RECIST 1.1 criteria, the patient has at least one measurable lesion (measurable lesion with a long diameter ≥ 10 mm on CT/MRI scan or lymph node lesion with a short diameter ≥ 15 mm on CT/MRI scan, and the measurable lesion has not received local treatment such as radiotherapy or cryotherapy).
• Expected survival time ≥ 6 months
• possess normal and sound organ function
• Females of childbearing age must agree to use contraceptive measures (such as intrauterine device, contraceptives or condoms) during the medication period and within 6 months after the end of medication; serum or urine pregnancy test is negative within 7 days before study enrollment, and must be a non-lactating patient; males must agree to use contraceptive measures during the study period and within 6 months after the end of the study.
• The subject has good compliance and is willing to cooperate with follow-up.

Exclusion criteria

• Previous radiotherapy, chemotherapy, concurrent chemoradiotherapy or other targeted therapy.
• Known hilar cholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and fibrolamellar carcinoma; other active malignant tumors except HCC within 5 years or concurrently.
• Hypertension that cannot be well controlled with antihypertensive drugs (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg); previous hypertensive crisis or hypertensive encephalopathy.
• The subject has a history of other malignant tumors (except cured basal cell carcinoma of the skin and carcinoma in situ of the cervix) or concurrent malignant tumors.
• Previous treatment with Iparomlimab and Tuvonralimab or other PD-1/PD-L1/CTLA-4 inhibitors; known previous allergy of the subject to macromolecular protein preparations or any component of Iparomlimab and Tuvonralimab.
• The subject has any active autoimmune disease or a history of autoimmune disease (such as, but not limited to: autoimmune hepatitis, interstitial pneumonia, uveitis, enteritis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism); subjects with vitiligo or asthma that was completely relieved in childhood and does not require any intervention in adulthood can be included; subjects with asthma requiring medical intervention with bronchodilators cannot be included.
• The subject is using immunosuppressants, or systemic or absorbable local hormone therapy for immunosuppressive purposes (dose > 10 mg/day prednisone or other hormones with equivalent efficacy), and continues to use them within 2 weeks before enrollment.
• Clinically symptomatic ascites or pleural effusion requiring therapeutic paracentesis or drainage.
• Uncontrolled clinical symptoms or diseases of the heart, such as: Heart failure of NYHA Class II or above；Unstable angina pectoris；Myocardial infarction within 1 year；Patients with clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.
• The patient currently (within 3 months) has esophageal varices, active gastroduodenal ulcer, ulcerative colitis, portal hypertension and other digestive tract diseases, or active bleeding from unresected tumors, or other conditions judged by the investigator that may cause gastrointestinal bleeding or perforation.
• Previous or current severe bleeding (bleeding > 30 ml within 3 months), hemoptysis (> 5 ml of fresh blood within 4 weeks) or thromboembolic events (including stroke events and/or transient ischemic attack) within 12 months.
• The subject has an active infection or unexplained fever > 38.5 ℃ during screening or before the first dose (fever caused by tumor can be included as judged by the investigator).
• Patients with objective evidence of previous or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe impairment of lung function, etc.
• The subject has congenital or acquired immunodeficiency, such as HIV infection, or active hepatitis (transaminase does not meet the inclusion criteria; for hepatitis B: HBV DNA ≥ 10⁴/ml; for hepatitis C: HCV RNA ≥ 10³/ml); chronic hepatitis B virus carriers with HBV DNA < 2000 IU/ml (< 10⁴ copies/ml) can be enrolled only if they receive antiviral treatment during the trial.
• Live vaccine接种 within 4 weeks before study medication or likely to be vaccinated during the study period.
• The subject has a known history of psychotropic drug abuse, alcoholism or drug addiction.
• The investigator deems that the subject should be excluded from this study, for example, as judged by the investigator, the subject has other factors that may lead to the forced termination of the study in the middle, such as other serious diseases (including mental diseases) requiring combined treatment, severe laboratory test abnormalities, or family or social factors that may affect the safety of the subject or the collection of data and samples.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07515469 · E20251317A

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗