NCT05516628

Deep, Multi-omics Phenotyping to Predict Response, Resistance and Recurrence to Adjuvant Atezolizumab Plus Bevacizumab in Resected Hepatocellular Carcinoma

Deep, Multi-omics Phenotyping to Predict Response, Resistance and Recurrence to Adjuvant Atezolizumab Plus Bevacizumab in Resected Hepatocellular Carcinoma (HCC)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: National Cancer Centre, Singapore · Academic / Other
• Sex: All
• Age: 21 Years – 90 Years
• Healthy volunteers: Not accepted

Summary

Hepatocellular carcinoma (HCC) is the 7th most common cancer worldwide but is the 4th deadliest, because diagnosis tend to be late and current systemic therapies are poorly efficacious. Within the same tumour, different parts of the HCC can belong to separate molecular sub-groups. In addition, there is currently no validated predictive biomarkers to help clinicians select the best therapy for an individual patient. This challenge poses an urgent, unmet clinical need. To address this, the multi-disciplinary research program Precision Medicine in Liver Cancer across an Asia-Pacific Network (PLANet 1.0) was conceptualized and successfully conducted from 2016-22. The program uncovered novel insights into the highly heterogeneous molecular landscape of HCC and novel mechanisms, including how HCC reverts to fetal forms to escape the body's immunological defence. These investigations will be continued in PLANet 2.0 and in this new phase, the research team will investigate patients receiving best-in-class therapeutics in 2 investigator-initiated clinical studies (AHCC12 and AHCC13), including Atezolizumab plus Bevacizumab (Atezo+Bev) and Yttrium-90, which allows the research team to collect longitudinal, before and after treatment biosamples and clinical data. These clinical studies will serve as proof-of-concept to the study team's translational findings and allow it to uncover predictive biomarkers which will help clinicians to institute more efficacious and personalized treatment in the future. The research team comprises of experts in different complementary fields (epigenomics, genomics, immunomics, metabolomics, proteomics, clinical science and data science) and across different institutions. This allows the team to adopt an integrative approach in understanding the landscape of the HCC tumour micro-environment and biomarkers co-localisation, and their role in tumour evolution and therapeutic response. By adopting a wide spectrum of converging investigations, PLANet 2.0 will identify and validate biomarkers that correlate with clinical outcomes (response, resistance and recurrence).

Detailed description

This is a clinical translational study on a prospective, interventional clinical cohort (defined as the AHCC12 study). Patients at high risk of HCC recurrence will receive adjuvant Atezolizumab plus Bevacizumab every 3-weekly for two years following surgery. Serially collected biosamples will be deeply-phenotyped and correlated with treatment outcomes (recurrence vs non-recurrence).

Conditions

• Hepatocellular Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Surgical Resection	Resection of Primary Hepatocellular Cancer Tumour.
DRUG	Adjuvant Atezolizumab-Bevacizumab Therapy	Patient receives adjuvant Atezolizumab plus Bevacizumab every 3-weekly for two years following resection of hepatocellular carcinoma tumour.

Timeline

• Start date: 2023-02-28
• Primary completion: 2027-03-01
• Completion: 2027-03-01
• First posted: 2022-08-25
• Last updated: 2025-06-17

Locations

6 sites across 1 country: Singapore