Neoadjuvant Therapy in Patients With Resectable HCC Screened by a Multimodal Deep Learning Model

Chen Xiaoping

Status and phase: Enrolling; Phase 2

Conditions: HCC

Treatments: Procedure: Hepatic arterial infusion chemotherapy; Drug: Lenvatinib; Drug: Tislelizumab; Procedure: Liver resection

Study type: Interventional

Funder types: Other

Identifiers

NCT06420440

Neoadj-Net01

Details and patient eligibility

About

Primary liver cancer is one of the most common malignant tumors in the world, and about 80%~90% of primary liver cancers are pathologically characterized as hepatocellular carcinoma (HCC). Radical surgery is the main method for patients with HCC to obtain long-term survival. However, the early recurrence rate of high-risk HCC is very high, which seriously affects the overall therapeutic effect.

Full description

The protocol was revised in April 2025 (V1.1). Primary liver cancer is one of the most common malignant tumors in the world, and about 80%~90% of primary liver cancers are pathologically characterized as hepatocellular carcinoma (HCC). Radical surgery is the main method for patients with HCC to obtain long-term survival. However, the early recurrence rate of high-risk HCC is very high, which seriously affects the overall therapeutic effect. Although the tumor is in BCLC-A stage, when the tumor diameter is more than 5cm, the effect of surgery is worse than that of single small HCC due to the large resection range, the high risk of surgery and residual disease. In addition, BCLC-stage B and C tumors have a high recurrence rate due to multiple lesions or macrovascular invasion. To address this issue, new tools are urgently needed to guide the selection of appropriate treatment regimens to reduce the risk of postoperative recurrence and improve overall survival.

The investigators multidisciplinary team used deep learning technology to construct an artificial intelligence prediction model of neoadjuvant therapy (Neoadj-Net) benefit based on pre-treatment genetic testing data, digital pathology slides and imaging data (enhanced MRI) of 536 intermediate-stage HCC patients treated with HAIC in combination with lenvatinib and PD-1 monoclonal antibody in six centers, and external center data validated the model's good ability to identify the beneficiary population of the combination regimen ( AUC 0.89, Accuracy 0.86). This study is to explore the effectiveness and safety of Neoadj-Net in reducing postoperative recurrence by observing the benefit of the combined neoadjuvant regimen in patients who are potentially benefited from neoadjuvant therapy and direct surgery from the perspective of precision therapy.

Enrollment: 160 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Aged 18-75.
2. No previous local or systemic treatment for hepatocellular carcinoma.
3. Child-Pugh liver function score ≤ 7.
4. ECOG PS 0-1.
5. No serious organic diseases of the heart, lungs, brain, kidneys, etc.
6. Enhanced MRI determines that the tumor is technically resectable but at high risk for recurrence(BCLC-A tumor diameter more than or equal to 5cm; BCLC-B; BCLC-C) ; without distant metastasis.
7. Pathologic type of hepatocellular carcinoma confirmed by puncture biopsy.
8. Multimodal Deep Learning Model Screening Based on Pathology, Imaging, and Genetic Data Suggests Benefit from HAIC in Combination with Lenvatinib and PD-1 inhibitors.

Exclusion criteria

1. Pregnant and lactating women.
2. Suffering from a condition that interferes with the absorption, distribution, metabolism, or clearance of the study drug (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, impaired absorption, etc.).
3. A history of gastrointestinal bleeding within the previous 4 weeks or a definite predisposition to gastrointestinal bleeding (e.g., known locally active ulcer lesions, fecal occult blood ++ or more, or gastroscopy if persistent fecal occult blood +) that has not been targeted, or other conditions that may have caused gastrointestinal bleeding (e.g., severe fundoplication/esophageal varices), as determined by the investigator.
4. Active infection.
5. Other significant clinical and laboratory abnormalities that affect the safety evaluation.
6. Inability to follow the study protocol for treatment or follow up as scheduled.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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160 participants in 2 patient groups

Neoadjuvant therapy group

Experimental group

Description:

Patients in the neoadjuvant group received neoadjuvant therapy prior to surgery (two cycles of HAIC combined with Tislelizumab and Lenvatinib), and adjuvant therapy (Tislelizumab for 8 cycles) after surgery.

Treatment:

Procedure: Liver resection

Drug: Tislelizumab

Drug: Tislelizumab

Drug: Lenvatinib

Procedure: Hepatic arterial infusion chemotherapy

Direct liver resection group

Active Comparator group

Description:

Patients in the control group underwent liver resection directly and received adjuvant therapy (Tislelizumab for 8 cycles) after surgery.

Treatment:

Procedure: Liver resection

Drug: Tislelizumab

Drug: Tislelizumab