Neoadjuvant liver‑artery chemotherapy plus PD‑1 immunotherapy, then PD‑1 after surgery, for high‑risk recurrent liver cancer

Neoadjuvant Hepatic Arterial Infusion Chemotherapy Plus Tislelizumab Combined With Adjuvant Tislelizumab in Preventing Postoperative Recurrence for High-risk Hepatocellular Carcinoma: a Prospective, Single-arm, Phase II Clinical Study

This trial tests whether giving hepatic arterial infusion chemotherapy (HAIC) with PD‑1 immunotherapy before surgery, then continuing PD‑1 after surgery, helps people with resectable hepatocellular carcinoma beyond Milan criteria.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 39 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Sun Yat-sen University (other)
• Drugs / interventions: immunotherapy, Tislelizumab, chemotherapy
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06467799 on ClinicalTrials.gov

What this trial studies

This is a phase 2, single‑center interventional trial enrolling patients with newly diagnosed, resectable hepatocellular carcinoma beyond Milan criteria (e.g., single tumor >5 cm or 2–3 tumors with the largest >3 cm) and preserved liver function. Participants receive neoadjuvant hepatic arterial infusion chemotherapy (HAIC) combined with PD‑1 immunotherapy, proceed to surgical resection if eligible, and then receive adjuvant PD‑1 therapy after surgery. Key eligibility requires no vascular invasion or distant/lymph node metastasis, Child‑Pugh A liver function, KPS ≥90, and adequate residual liver volume (>40%). The main goal is to increase surgical curability and reduce early postoperative recurrence rates compared with historical outcomes.

Who should consider this trial

Good fit: Ideal candidates are newly diagnosed, untreated patients with resectable HCC beyond Milan criteria (CNLC Ib/IIa), Child‑Pugh A liver function, good performance status (KPS ≥90), sufficient future liver remnant (>40%), and no tumor thrombus or distant/lymph node metastasis.

Not a fit: Patients with tumor thrombus, distant metastases, poor liver function, low performance status, inadequate residual liver volume, or those who are not surgical candidates are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could lower postoperative recurrence and improve long‑term survival for patients with high‑risk resectable HCC.

How similar studies have performed: Early reports from the investigators' center and other groups suggest HAIC combined with immunotherapy can shrink tumors and show promise, but the combined neoadjuvant-plus‑adjuvant PD‑1 approach remains relatively novel and not yet widely validated in randomized trials.

Eligibility criteria

Inclusion Criteria:

1. Newly diagnosed and untreated hepatocellular carcinoma (clinical diagnostic criteria based on the " Chinese Guidelines for the Diagnosis and Treatment of Hepatocellular Carcinoma (2024 Edition) " formulated by the National Health Commission of China and the Barcelona Clinic Liver Cancer (BCLC) strategy for prognosis prediction and treatment recommendation of the European Association for the Study of the Liver (EASL));
2. Tumor staging: beyond Milan criteria (single tumor \>5 cm, or 2-3 tumors with the largest diameter \>3 cm), resectable CNLC stage Ib/IIa hepatocellular carcinoma;
3. No tumor thrombus, distant metastasis, or lymph node metastasis;
4. Normal liver volume ≥ 700 cc, estimated residual liver volume \>40% after resection;
5. Patient KPS ≥ 90;
6. Liver function Child-Pugh class A;
7. Estimated survival of more than 6 months;
8. Function of important organs meets the following requirements: white blood cells ≥ 4.0×10\^9/l, neutrophils ≥ 1.5×10\^9/l, platelets ≥ 80.0×10\^9/l, hemoglobin ≥ 90 g/l; serum albumin ≥ 2.8 g/dl; total bilirubin ≤ 1.5 × ULN, ALT/AST/ALP ≤ 2.5 × ULN; serum creatinine ≤ 1.5 × ULN or creatinine clearance rate \> 60 mL/min; no severe organic diseases;
9. The subject must be able to understand and voluntarily sign a written informed consent form, and must sign the informed consent form prior to any specific procedure of the study, agreeing to comply with the medication and postoperative follow-up requirements as designed in this study.

Exclusion Criteria:

1. Combined with severe impairment of functions of other important organs such as heart, lungs, and kidneys; active infections other than viral hepatitis or other serious comorbid conditions, making the patient unable to tolerate treatment;
2. Contraindications to surgical resection and immunotherapy;
3. History of other malignant tumors;
4. Combined with immunological diseases or other conditions requiring long-term steroid treatment;
5. Known or suspected allergy to the study drug or any drugs administered in connection with this trial;
6. History of organ transplantation;
7. Pregnant or breastfeeding women;
8. Other factors that may affect patient enrollment and assessment outcomes;
9. Refusal to follow-up according to the requirements set by the study protocol, and refusal to sign the informed consent form.

Where this trial is running

Guangzhou, Guangdong

• Sun Yat-sen University Cancer Center — Guangzhou, Guangdong, China (RECRUITING)

Study contacts

• Principal investigator: Yaojun Zhang, MD, PHD — Sun Yat-Sen University Cancer Center
• Study coordinator: Yaojun Zhang, MD, PHD

Conditions: Hepatocellular Carcinoma, Beyond Milan Criteria