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

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).

Conditions

• Hepatocellular Carcinoma

Interventions

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.

Sponsors & Collaborators

• Singapore General Hospital

  collaborator OTHER

• National University Hospital, Singapore

  collaborator OTHER

• Changi General Hospital

  collaborator OTHER

• Sengkang General Hospital

  collaborator OTHER

• Tan Tock Seng Hospital

  collaborator OTHER

• Singapore Clinical Research Institute

  collaborator OTHER

• Genome Institute of Singapore

  collaborator OTHER

• Institute of Molecular and Cell Biology of Singapore

  collaborator UNKNOWN

• Cancer Science Institute of Singapore

  collaborator UNKNOWN

• Duke-NUS Graduate Medical School

  collaborator OTHER

• Singapore Phenome Centre

  collaborator UNKNOWN

• Nanyang Technological University

  collaborator OTHER

• NMRC OF-LCG (OFLCG21Jun-0016)

  collaborator UNKNOWN

• National Cancer Centre, Singapore

  lead OTHER

Principal Investigators

• Pierce CHOW, MD, PhD · National Cancer Centre, Singapore

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

21 Years

Max Age

90 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-02-28

Primary Completion

2027-03-31

Completion

2027-03-31

Countries

• Singapore

Study Locations