Heterogeneity of Treatment Effects of Adding Locoregional Therapies to Atezolizumab Plus Bevacizumab in Patients With Unresectable Hepatocellular Carcinoma (ISMIO-026)

NCT07824765 | Not Yet Recruiting

• 1 other identifier: ISMIO-026
• Study Type: observational
• Target: 2,658
• Locations: 1 country
• Sites: 1

Brief Summary

uHCC imposes a substantial disease burden in China and the Asia-Pacific region. Atezo+Bev is an important first-line regimen for patients who have not received prior systemic therapy; however, not all patients achieve adequate and durable tumor control. In clinical practice, ablation, radiotherapy, or transarterial therapy is often added to Atezo+Bev to intensify intrahepatic disease control. The indications, timing, efficacy, and risk of liver-function impairment vary across LRTs. Most existing studies report average treatment effects and often use TACE as a fixed backbone, and therefore do not directly identify which patients receiving Atezo+Bev should receive early LRTs. Using target trial emulation and HTE analysis, this study will integrate baseline clinical variables with pretreatment contrast-enhanced CT/MRI features to estimate the CATE of early LRT initiation and identify patients likely to achieve greater survival benefit.

Conditions

Unresectable Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Overall survival

  With OS as the primary outcome, to estimate the overall treatment effect and CATE of initiating LRTs within 60 days after Atezo+Bev initiation versus not initiating LRTs within 60 days; and to integrate baseline clinical variables with multiregional radiomic, dynamic/habitat, and deep representation features from pretreatment contrast-enhanced CT/MRI to develop and validate an HTE decision model.

  through study completion, an average of 1 year

Secondary Outcomes (3)

• Model calibration

  through study completion, an average of 1 year

• Benefit ranking

  through study completion, an average of 1 year

• PFS/mPFS

  through study completion, an average of 1 year

Other Outcomes (1)

• Adverse event

  through study completion, an average of 1 year

Study Arms (4)

Training Cohort

Retrospective validation cohort

Prospective validation cohort

Biological validation cohort

Eligibility Criteria

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

Study Population

Adults with uHCC who initiate first-line Atezo+Bev and have received no prior systemic therapy for HCC.

You may qualify if:

• Age ≥18 years on the index date.
• Receipt of at least one dose each of atezolizumab and bevacizumab as part of the same first-line combination regimen, with an interval of ≤28 days between the first administrations of the two drugs.
• At least one intrahepatic lesion amenable to a protocol-specified LRT on the index date, with no absolute contraindication to Atezo+Bev or to all feasible LRTs.
• A clinical, radiologic, or pathologic diagnosis of uHCC on or before the index date; baseline EHS is permitted.
• Survival status or the date last known alive after the index date can be ascertained.
• No systemic therapy for HCC before the regimen initiation date.
• No LRT within 60 days before the index date or between baseline imaging and the index date; earlier prior LRTs are permitted provided that an untreated, measurable intrahepatic lesion remains.
• A technically adequate baseline contrast-enhanced CT/MRI examination and at least one untreated intrahepatic lesion that can be delineated and evaluated.
• Baseline ECOG performance status of 0-2.

You may not qualify if:

• Another primary malignancy requiring active systemic treatment on the index date, except for a malignancy that has been cured and has a low risk of recurrence.
• Participation on the index date in an interventional study that could affect treatment allocation or outcome assessment.
• Suitability for immediate curative resection or liver transplantation following multidisciplinary assessment.
• An absolute contraindication to Atezo+Bev or to all feasible LRTs.
• Active autoimmune disease or immunodeficiency requiring systemic immunosuppression or constituting a contraindication to atezolizumab.
• Inadequately controlled high-risk esophageal/gastric varices, recent variceal bleeding, an uncorrected bleeding tendency, or clinically significant coagulopathy.
• Inability to determine the index date, primary treatment strategy, OS outcome/censoring date, or absence of a technically adequate baseline contrast-enhanced CT/MRI examination.

Sponsors & Collaborators

• Zhongda Hospital: lead

Study Sites (1)

Zhongda hospital

Nanjing, Jiangsu, 213003, China

Location

Central Study Contacts

Jian Lu

CONTACT

13616106021; lujian43307131@126.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 36 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Study Record Dates

• First Submitted: September 1, 2026
• First Posted: September 17, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 17, 2026

Record last verified: 2026-09

Locations

CN (1)