Development and Prospective Validation of a Heterogeneous Treatment Effect-Based Decision Model for Transarterial Chemoembolization Combined With or Without Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma

Southeast University

Status: Not yet enrolling

Conditions: HCC - Hepatocellular Carcinoma

Treatments: Device: Heterogeneous Treatment Effect-Based Decision Model

Study type: Interventional

Funder types: Other

Identifiers

NCT07109336

ISMIO2501

Details and patient eligibility

About

Unresectable hepatocellular carcinoma (uHCC) constitutes a significant health burden in the Asia-Pacific (APAC) region, particularly in China, where it is frequently associated with hepatitis B virus (HBV) infection and diagnosed at advanced stages.

Transarterial chemoembolization (TACE) remains the standard treatment for intermediate-stage hepatocellular carcinoma (HCC), though its effectiveness diminishes in unresectable HCC (uHCC) with intermediate-to-high tumor burden. The IMbrave150 trial established atezolizumab plus bevacizumab (Atezo+Bev) as a superior alternative to sorafenib, demonstrating significant survival advantages in uHCC. Given the marked heterogeneity of intermediate-stage HCC, TACE may not benefit all patients equally. The TALENTACE study investigated on-demand TACE combined with Atezo+Bev versus TACE alone in treatment-naïve uHCC patients with intermediate-to-high tumor burden across China and Japan. Results revealed a statistically significant and clinically meaningful improvement in the primary endpoint, TACE- progression-free survival (PFS), though overall survival (OS) remained immature at the time of analysis.

This situation establishes a critical and unmet need for randomized controlled trials (RCTs) combined with extensive real-world evidence (RWE) to facilitate the assessment of individualized treatment heterogeneity and provide precise treatment recommendations in China and select Asia-Pacific regions.

Enrollment: 790 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• • Aged≥18 years

  • Initiated first-line Atezo+Bev.
  • Eligible for TACE treatment or received at least one TACE within ±2 months of Atezo+Bev initiation (before Atezo+Bev start, anytime during Atezo+Bev therapy, or after Atezo+Bev discontinuation).
  • Clinically or pathologically diagnosed uHCC before or at the initiation of Atezo/Bev.The evidence of being diagnosed as "unresectable" may include but is not limited to below:

"Unresectable" or "advanced" directly documented in the medical records History of extrahepatic metastasis as evidenced clinically or by radiology, histology or cytology OR China Liver Cancer (CNLC) Stage IIIb

• At least one visit record after the initiation of Atezo+Bev
• No prior systemic therapy for HCC, especially immunotherapy
• No prior locoregional therapy to the target lesion(s)
• At least one measurable untreated lesion
• ECOG Performance Status of 0-2

Exclusion criteria

• • Evidence of extrahepatic spread (EHS)

  • Participating in interventional clinical trials.
  • Being a candidate for curative treatments
  • Any condition representing a contraindication to TACE as determined by the investigators
  • Active or history of autoimmune disease or immune deficiency
  • Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high risk for bleeding
  • A prior bleeding event due to esophageal and/or gastric varices within 6 months prior to initiation of study treatment
  • Evidence of bleeding diathesis or significant coagulopathy
  • Missing critical baseline or outcome data

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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790 participants in 2 patient groups

Heterogeneous Treatment Effect-Based Decision Model

Active Comparator group

Description:

Participations receiving TACE alone or TACE combined with Atezolizumab plus Bevacizumab decsided by Heterogeneous Treatment Effect-Based Decision Model

Treatment:

Device: Heterogeneous Treatment Effect-Based Decision Model

TACE combined with Atezolizumab plus Bevacizumab

Active Comparator group

Description:

Participations all receiving TACE combined with Atezolizumab plus Bevacizumab

Treatment:

Device: Heterogeneous Treatment Effect-Based Decision Model