DYNAmic Immune Microenvironment of HCC Treated With atezolIzumab Plus bevaCizumab

NCT04954339 | Active Not Recruiting Phase 2

• 1 other identifier: 2021-0785
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Part I (Clinical trial setting): A single-arm phase II study to investigate the efficacy of neoadjuvant atezolizumab (T) + bevacizumab (A) in patients with potentially resectable BCLC stage B/C or high risk resectable hepatocellular carcinoma (HCC) (n = 45) Part II (Biomarker study setting): Exploratory translational research will be conducted using samples obtained from Part 1 (n =45) and those acquired from an independent cohort of treatment-naïve HCC patients (n = 15).

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (2)

• The rate of major pathological response

  Part I\_The rate of major pathological response (MPR) rate defined by \<10% of residual viable tumor in the tumor bed

  Through treatment discontinuation, an average of 6 months

• Distinct immunophenotypes and dynamic changes of tumor-infiltrating immune cells by single nucelar RNA-sequencing, single cell RNA sequencing, spatial transcriptomics, multiplexed immunohistochemistry (mIHC), flow cytometry (and/or CyTOF)

  Part II\_Rate of single nucelar RNA-sequencing, single cell RNA sequencing, spatial transcriptomics, multiplexed immunohistochemistry (mIHC), flow cytometry (and/or CyTOF)

  up to 36 months

Secondary Outcomes (10)

• The rate of completion of treatment and resection

  Through treatment discontinuation, an average of 6 months

• The rate of R0 resection

  Through treatment discontinuation, an average of 6 months

• Incidence and severity of adverse events, with severity determined according to Common Terminology Criteria for Adverse Events v5.0

  up to 36 months

• Progression-free survival (PFS)

  up to 36 months

• Radiological response

  From enrol to surgical resection, an average 6 months

Study Arms (1)

Atezolizumab plus Bevacizumab

EXPERIMENTAL

Two cycles of naeoadjuvant atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) prior to surgical resection and four cycles of adjuvant atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) after the surgery will be administered.

Drug: Aatezolizumab plus Bevacizumab

Interventions

Aatezolizumab plus Bevacizumab DRUG

Two cycles of naeoadjuvant atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) prior to surgical resection and four cycles of adjuvant atezolizumab (1200 mg) plus bevacizumab (15 mg/kg) after the surgery will be administered.

Also known as: Ticentriq plus Avastin

Atezolizumab plus Bevacizumab

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acquisition of Signed Informed Consent Form prior to any study specific procedures
• Willingness and ability to comply with the study protocol
• ≥ 19 years of age at the time of signing Informed Consent Form
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
• Histologically or cytologically confirmed HCC
• Child-Pugh class A (Child-Pugh score of 5 or 6) assessed within 7 days
• Negative HIV test at screening
• Documented virology status of hepatitis, as confirmed by screening HBV and HCV serology test
• For patients with active hepatitis B virus (HBV): HBV DNA \< 500 IU/mL obtained within 28 days prior to initiation of study treatment, and Anti-HBV treatment (per local standard of care; e.g., entecavir) for a minimum of 14 days prior to study entry and willingness to continue treatment for the length of the study
• Potentially resectable Barcelona Clinic Liver Cancer (BCLC) stage B/C meeting any of the following criteria by 4-phase liver dynamic computed tomography (CT) or gadoxetic-acid enhanced magnetic resonance imaging (MRI) or chest CT with enhancement
• Portal vein invasion (Vp1, Vp2 and Vp3)
• Hepatic vein invasion (Vv1 and Vv2)
• Lymph node metastasis
• multiple tumor nodules (n ≥ 2)
• Solitary distant metastasis or Resectable HCC meeting any of the following criteria by 4-phase liver dynamic CT or gadoxetic-acid enhanced MRI

You may not qualify if:

• Extrahepatic metastases that are not candidates for treatment of curative aim (e.g. resection, radiation or radiofrequency ablation)
• Presence of central nervous system (CNS) metastases
• Concurrent or previous history of another primary cancer within 3 years prior to study treatment except for curatively treated cervical cancer in situ, non-melanomatous skin cancer, superficial bladder cancer (pTis or pT1) and curatively treated thyroid cancer of any stage. Concurrent, histologically confirmed, unresected thyroid cancer without distant metastasis could be allowed with the agreement of the principal investigator.
• Chronic hepatitis B, defined as HBV DNA (\> 2,000 IU / mL) and ALT\> upper limit of normal range, must be treated with antiviral drugs before enrollment to reach appropriate viral suppression (HBV DNA \<2000 IU / mL), and the antiviral drugs must be maintained during the study treatment period and for 6 months after the last dose of study treatment.
• Prior systemic therapy for metastatic disease including systemic investigational agents
• Uncontrolled medical illness: including medically uncontrolled infection, uncontrolled hypertension, unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months
• Current or recent (within 10 days of start of study treatment) use of aspirin (\>325mg/day), clopidogrel (\>75mg/day), oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes (therapeutic anticoagulation on a stable dose for at least 2 weeks prior to the start of study treatment is allowed)
• Known alcohol or drug abuse- Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment.
• Patients receiving prophylactic antibiotics (e.g., to prevent a urinary tract infection or chronic obstructive pulmonary disease exacerbation) are eligible for the study.
• Inadequately controlled hypertension (defined as systolic blood pressure \>150mmHg and/or diastolic blood pressure \>100mmHg)
• Prior history of hypertensive crisis or hypertensive encephalopathy
• History or evidence upon physical or neurological examination of CNS disease (e.g. seizures) unrelated to cancer unless adequately treated with standard medical therapy
• Significant vascular disease (e.g. aortic aneurysm requiring surgical repair or recent arterial thrombosis) within 6 months of start of study treatment
• Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident within 3 months prior to initiation of study treatment), unstable arrhythmia, or unstable anginanginaa

Sponsors & Collaborators

• Tae Won Kim: lead

Study Sites (1)

Asan Medical Center

Seoul, Songpa, 138736, South Korea

Location

Related Publications (5)

• Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.

  PMID: 30207593 BACKGROUND

• El-Serag HB. Hepatocellular carcinoma. N Engl J Med. 2011 Sep 22;365(12):1118-27. doi: 10.1056/NEJMra1001683. No abstract available.

  PMID: 21992124 BACKGROUND

• Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet. 2012 Mar 31;379(9822):1245-55. doi: 10.1016/S0140-6736(11)61347-0. Epub 2012 Feb 20.

  PMID: 22353262 BACKGROUND

• Heimbach JK, Kulik LM, Finn RS, Sirlin CB, Abecassis MM, Roberts LR, Zhu AX, Murad MH, Marrero JA. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2018 Jan;67(1):358-380. doi: 10.1002/hep.29086. No abstract available.

  PMID: 28130846 BACKGROUND

• Chan AWH, Zhong J, Berhane S, Toyoda H, Cucchetti A, Shi K, Tada T, Chong CCN, Xiang BD, Li LQ, Lai PBS, Mazzaferro V, Garcia-Finana M, Kudo M, Kumada T, Roayaie S, Johnson PJ. Development of pre and post-operative models to predict early recurrence of hepatocellular carcinoma after surgical resection. J Hepatol. 2018 Dec;69(6):1284-1293. doi: 10.1016/j.jhep.2018.08.027. Epub 2018 Sep 18.

  PMID: 30236834 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Tae Won Kim

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PhD

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: July 8, 2021
• Study Start: October 29, 2021
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 31, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)