ClinicalTrials.gg
Not yet recruitingNCT07824765Updated Sep 17, 2026

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

An observational study in Unresectable Hepatocellular Carcinoma, sponsored by Zhongda Hospital. Not yet recruiting at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-17.

Sponsored by Zhongda Hospital · Observational

Study type
Observational
Model
Cohort
Time perspective
Prospective
Enrollment
2,658
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

  • Unresectable Hepatocellular Carcinoma
03

In context

Carcinoma, Hepatocellular

3,648 studies on the registry are indexed under Carcinoma, Hepatocellular; 1,061 are open to participants now.

This study's planned enrollment of 2,658 is above the median of 200 across 850 observational studies indexed under Carcinoma, Hepatocellular.

Browse Carcinoma, Hepatocellular studies →

Lead sponsor

Zhongda Hospital is the lead sponsor of 104 studies on the registry; 42 are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
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.

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Age ≥18 years on the index date.
  • Receipt of at least one dose each of atezolizumab and bevacizumab as part of the same 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 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 performance status of 0-2.

Exclusion criteria

Exclusion Criteria:

  • Another primary 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 to Atezo+Bev or to all feasible LRTs.
  • Active disease or immunodeficiency requiring systemic or constituting a contraindication to atezolizumab.

Inadequately controlled high-risk esophageal/gastric varices, recent variceal bleeding, an uncorrected bleeding tendency, or 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.
Terms in these criteria, in plain language(7)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Line of therapy

A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.

“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

05

Study design

Observational model
Cohort
Time perspective
Prospective
Enrollment
2,658 participants (estimated)
Target follow-up
36 Months
Patient registry
Yes

Groups and cohorts

  • Training Cohort
  • Retrospective validation cohort
  • Prospective validation cohort
  • Biological validation cohort

This study also gives Atezolizumab. No intervention listed here names it: that was found by reading the record.

06

What researchers measure

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.

    Time frame: through study completion, an average of 1 year

Secondary outcomes

  1. Model calibration

    Time frame: through study completion, an average of 1 year

  2. Benefit ranking

    Time frame: through study completion, an average of 1 year

  3. PFS/mPFS

    Defined as the time from index date to the first occurrence of disease progression or death from any cause (whichever occurs first), as determined by the investigator according to RECIST v1.1 or mRECIST.

    Time frame: through study completion, an average of 1 year

Other outcomes

  1. Adverse event

    To describe and compare the spectrum and severity of AEs between the two strategies and within their subgroups, with particular attention to hemorrhage, hypertension, hepatotoxicity, immune-related AEs, and complications associated with each type of LRT.

    Time frame: through study completion, an average of 1 year

07

Study locations

1 site
08

References and documents

Individual participant data

Plan to share: Undecided

No publications or documents are linked to this record.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 17, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT07824765
Lead sponsor
Zhongda Hospital
Responsible party
Jian Lu (Prof., Zhongda Hospital) — Principal investigator
First posted
Sep 17, 2026
Start date
Sep 1, 2026 (estimated)
Primary completion
Sep 1, 2027 (estimated)
Completion
Dec 31, 2027 (estimated)
Last update
Sep 17, 2026

Study contacts

Jian Lu
Contact
lujian43307131@126.com
13616106021

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is not yet recruiting, as verified in Sep 2026. You cannot join it, but the record below documents what was studied.

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Discussion

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