FAD Subtype-Guided Combination Therapy for Unresectable Hepatocellular Carcinoma

NCT07314372 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: FAD-HCC-001
• Study Type: interventional
• Target: 86
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a prospective, multicenter Phase II trial evaluating a personalized treatment strategy for patients with unresectable hepatocellular carcinoma (HCC). The study uses a metabolic classification system called the fatty acid degradation (FAD) subtype to guide therapy selection. Patients will be assigned to different treatment groups based on their tumor's FAD subtype, determined through RNA-seq analysis of the tumor tissue obtained from liver biopsy.

Conditions

Unresectable Hepatocellular Carcinoma (HCC); Hepatocellular Carcinoma (HCC); Liver Cancer Adult

Keywords

Hepatocellular Carcinoma; Fatty Acid Degradation; Metabolic Subtyping; Precision Medicine; Conversion Therapy; Immunotherapy; Anti-angiogenic Therapy; TACE

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  ORR is defined as the proportion of participants who achieve a confirmed complete response (CR) or partial response (PR) according to RECIST v1.1, as assessed by imaging every 6 weeks. ORR will be calculated separately for each FAD subtype cohort (F1/F2 and F3).

  From first dose until first documented disease progression or death, whichever occurs first, assessed up to 24 months.

Secondary Outcomes (7)

• Objective Response Rate (ORR) by mRECIST

  From first dose until first documented disease progression or death, whichever occurs first, assessed up to 24 months.

• Disease Control Rate (DCR)

  From first dose until first documented disease progression or death, whichever occurs first, assessed up to 24 months.

• Progression-Free Survival (PFS)

  From first dose until radiographic disease progression or death, whichever occurs first, assessed up to 24 months.

• Overall Survival (OS)

  From first dose until death from any cause, assessed up to 24 months.

• Duration of Response (DoR)

  From first documented response (CR or PR) until disease progression or death, whichever occurs first, assessed up to 24 months.

Other Outcomes (4)

• Correlation Between MRI-Derived Fat Fraction and Transcriptomic FAD Subtype Score

  From baseline tissue/MRI assessment until end of treatment, assessed up to 24 months.

• Correlation Between Molecular Biomarker Levels and Objective Tumor Response

  Baseline, on-treatment, and at disease progression (up to 24 months)

• Correlation Between Molecular Biomarker Levels and Treatment Response

  From baseline until disease progression, assessed up to 24 months.

Study Arms (2)

F1/F2 Subtype: Camrelizumab Plus Apatinib

EXPERIMENTAL

Participants whose tumors are classified as F1 or F2 based on the fatty acid degradation (FAD) subtype will receive systemic therapy with camrelizumab and apatinib. Camrelizumab is administered intravenously at 200 mg every 3 weeks, and apatinib is taken orally at 250 mg once daily. Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or completion of the planned treatment duration. Imaging assessments are conducted every 6 weeks to evaluate tumor response.

Drug: Camrelizumab Plus Apatinib

F3 Subtype: TACE Plus Camrelizumab and Apatinib

EXPERIMENTAL

Participants with the F3 metabolic subtype, characterized by high fatty acid degradation activity, will receive transarterial chemoembolization (TACE) in addition to systemic therapy. Camrelizumab (200 mg IV every 3 weeks) and apatinib (250 mg orally once daily) are administered on the same schedule as the F1/F2 arm. TACE is performed 2-4 weeks after systemic therapy initiation, with up to two treatments per tumor (maximum four sessions total). Apatinib is paused 3-5 days before TACE and restarted 3-5 days afterward. Treatment continues until disease progression, unacceptable toxicity, or discontinuation for clinical reasons. Imaging assessments occur every 6 weeks.

Drug: TACE Plus Camrelizumab and Apatinib

Interventions

Camrelizumab Plus Apatinib DRUG

Camrelizumab is administered intravenously at 200 mg every 3 weeks, and apatinib is taken orally at 250 mg once daily.

F1/F2 Subtype: Camrelizumab Plus Apatinib

TACE Plus Camrelizumab and Apatinib DRUG

Camrelizumab (200 mg IV every 3 weeks) and apatinib (250 mg orally once daily) are administered on the same schedule as the F1/F2 arm. TACE is performed 2-4 weeks after systemic therapy initiation, with up to two treatments per tumor (maximum four sessions total). Apatinib is paused 3-5 days before TACE and restarted 3-5 days afterward.

F3 Subtype: TACE Plus Camrelizumab and Apatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥18 years of age who voluntarily agree to participate and sign informed consent.
• Histologically or cytologically confirmed hepatocellular carcinoma (HCC).
• Unresectable or not suitable for curative local therapy, or progression after prior surgery or local therapy.
• BCLC stage B or C.
• No prior systemic therapy for HCC.
• At least one measurable lesion according to RECIST v1.1.
• Availability of fresh or archival tumor tissue for FAD subtype testing; if not available at screening, MRI fat fraction may be used temporarily.
• Child-Pugh class A or B (≤7 points).
• ECOG performance status 0-1.
• Adequate organ function, including:
• ANC ≥1.5 × 10⁹/L
• Platelets ≥75 × 10⁹/L
• Hemoglobin ≥90 g/L
• Albumin ≥30 g/L
• Total bilirubin ≤1.5 × ULN

You may not qualify if:

• Non-HCC primary liver cancers (e.g., cholangiocarcinoma, combined HCC-CCA).
• F3 subtype without liver lesions on imaging.
• Clinically significant ascites requiring therapeutic intervention, or uncontrolled pleural/pericardial effusion.
• Interstitial lung disease, pneumonitis requiring steroids, or active pulmonary infection.
• Active or history of autoimmune disease requiring systemic treatment (exceptions allowed per protocol, e.g., controlled hypothyroidism).
• Recent use (within 2 weeks) of systemic immunosuppressive therapy \>10 mg/day prednisone equivalent.
• Gastrointestinal bleeding within 6 months, high-risk varices, active ulcers, fistula, perforation, or intra-abdominal abscess.
• Known bleeding or clotting disorders; therapeutic anticoagulation not permitted.
• Thromboembolic events within 6 months (e.g., stroke, PE).
• Significant cardiovascular disease, including NYHA class ≥II heart failure, recent MI (within 1 year), unstable angina, clinically significant arrhythmias, or QTc prolongation.
• Uncontrolled hypertension (SBP ≥140 mmHg or DBP ≥90 mmHg despite treatment), or history of hypertensive crisis.
• Major vascular disease within 6 months (e.g., arterial thrombosis, aneurysm requiring repair).
• Serious non-healing wounds, active ulcers, or fractures.
• Inability to swallow oral medication or conditions affecting drug absorption.
• Severe infection within 4 weeks, therapeutic antibiotics within 14 days, fever ≥38.5°C within 7 days before enrollment, or WBC \>15 × 10⁹/L.

Sponsors & Collaborators

• The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School: lead

Study Sites (1)

Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School

Nanjing, Jiangsu, 210008, China

Location

Related Publications (2)

• Li B, Wen J, Xu Z, Yan P, Han B, Yu D. Comprehensive analysis of transcriptomic biomarkers for predicting response to atezolizumab plus bevacizumab immunotherapy in hepatocellular carcinoma. Clin Mol Hepatol. 2025 Jan;31(1):e31-e34. doi: 10.3350/cmh.2024.0628. Epub 2024 Sep 20. No abstract available.

  PMID: 39300923 BACKGROUND

• Li B, Li Y, Zhou H, Xu Y, Cao Y, Cheng C, Peng J, Li H, Zhang L, Su K, Xu Z, Hu Y, Lu J, Lu Y, Qian L, Wang Y, Zhang Y, Liu Q, Xie Y, Guo S, Mehal WZ, Yu D. Multiomics identifies metabolic subtypes based on fatty acid degradation allocating personalized treatment in hepatocellular carcinoma. Hepatology. 2024 Feb 1;79(2):289-306. doi: 10.1097/HEP.0000000000000553. Epub 2023 Aug 7.

  PMID: 37540187 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

camrelizumab; apatinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Officials

• Decai Yu, Doctor

  the Affiliated Drum Tower Hospital, Medical School of Nanjing University

  STUDY CHAIR

Central Study Contacts

Decai Yu, Doctor

CONTACT

+86-025-68182222; yudecai@nju.edu.cn

Yuan Cheng, Doctor

CONTACT

+8613915963713; 19656093@qq.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: November 22, 2025
• First Posted: January 2, 2026
• Study Start: February 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 20, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)