Ezurpimtrostat Autophagy Inhibitor in Association With Atezolizumab-Bevacizumab in First Line Treatment of Unresectable Hepatocellular Carcinoma

NCT05448677 | Terminated Phase 2 DMC

• 1 other identifier: 38RC21.0434
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

The study will assess the efficacy of Ezurpimtrostat in association with standard of care (Atezolizumab-Bevacizumab), compared to standard of care alone, as first line treatment in patients with unresectable hepatocellular carcinoma.The study drug which is tested is the Ezurpimtrostat in association with Atezolizumab-Bevacizumab to allow a better tumor response as well as better survival outcomes with an acceptable safety.

Conditions

Hepatocellular Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  Progression-Free Survival (PFS), defined as the time from randomization to the occurrence of disease progression or death from any cause, whichever occurs first. Progression events will be considered based on centralized tumor response assessment according to RECIST version 1.1 and PFS analyses will be performed by the CHU Grenoble Alpes Statistics department.

  At 36 months

Secondary Outcomes (1)

• Objective response rate (ORR)

  At 3,6,9,12 months

Study Arms (2)

Experimental

EXPERIMENTAL

Ezurpimtrostat+Atezolizumab-Bevacizumab

Drug: Ezurpimtrostat; Drug: Atezolizumab; Drug: Bevacizumab

Control

ACTIVE COMPARATOR

Atezolizumab-Bevacizumab

Drug: Atezolizumab; Drug: Bevacizumab

Interventions

Ezurpimtrostat DRUG

Patients in the experimental arm will be instructed to take their assigned oral dose every day.

Experimental

Atezolizumab DRUG

Atezolizumab will be administered by IV infusion at a fixed dose of 1200 mg on Day 1 of each 21-days cycle

Control; Experimental

Bevacizumab DRUG

Bevacizumab will be administered by IV infusion at a dose of 15 mg/kg on Day 1 of each 21-day cycle.

Control; Experimental

Eligibility Criteria

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

You may qualify if:

• Males or females ≥ 18 years of age
• Histologically confirmed (liver biopsy within 6 previous months) and documented non resectable or metastatic HCC
• No prior systemic therapy for advanced HCC
• Liver tumor burden\< 50% of the liver (per Investigator judgment)
• Child-Pugh A (≤ 6) without any history of cirrhotic decompensation within the past 6 months
• Antiviral therapy required in hepatitis B virus patients (Hepatitis B antigen positive)
• Presence of a measurable tumor per RECIST v1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Life expectancy ≥ 12 weeks
• Adequate hematologic function prior to the first dose of Ezurpimtrostat, defined as:
• Absolute neutrophils count ≥ 1500 cells/µL 11.2. Hemoglobin ≥ 9 g/dL with no transfusion within 4 weeks prior to first planned dose of Ezurpimtrostat 11.3. Platelet count \> 50,000/µL with no transfusion within 2 weeks prior to first planned dose of Ezurpimtrostat
• Adequate renal function prior to first dose, defined as 12.1. Serum creatinine \< 1.5 ULN 12.2. Creatinine clearance ≥ 30 mL/min/m2 (by Cockroft-Gault equation of 24-hour urine) if creatinine ≥ 1.5 X ULN
• Adequate hepatic function prior to first dose, defined as AST/ALT ≤ 5 X ULN
• Women patients of childbearing potential\* must have a negative blood pregnancy test at screening and baseline, and be willing to use a highly effective\*\* contraception. The patient should be advised to continue the contraception for at least 6 months following the completion of dosing. Women with cessation for \> 24 months of previously occurring menses, or women of any age who have had a hysterectomy, or have had both ovaries removed will be considered to be of non-childbearing potential
• Male patients of reproductive potential must be willing to use one acceptable method of contraception, as judged by Investigator and Sponsor, and to refrain from donating sperm from the time of screening through at least 6 months following the completion of dose administration

You may not qualify if:

• Any known history of encephalopathy
• Untreated or incompletely treated esophageal and/or gastric varices with bleeding or high-risk for bleeding
• Known esophageal varices with recent history of bleeding (within previous 6 months)
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
• Known fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC
• Chronic treatment with immunosuppressive agents (like steroids) ≤ 6 weeks prior to first planned dose of treatment
• Major surgical procedures, open biopsy or significant traumatic injury ≤ 4 weeks prior to first dose of treatment or anticipation of major surgical procedure during the course of the trial, minor surgical procedures ≤ 1 week of first planned dose
• Local therapy to liver within 28 days prior to initiation of study treatment or non-recovery from side effects of any such procedure
• Any clinically significant cardiovascular condition as judged by the Investigator (such as New York Heart Association Class II or greater cardiac failure, myocardial infarction, or cerebrovascular accident within 3 months prior to Day 1 of Cycle 1, inadequately controlled arterial hypertension, unstable arrhythmia, or unstable angina)
• Severe or uncontrolled renal condition
• Untreated chronic hepatitis B
• HCV infection
• Known history of immunodeficiency diseases (e.g., active HIV)
• Use of any prohibited concomitant medications within 14 days of the Baseline/Day 1 visit
• Contraindication to additional liver biopsy planned between C4 and C5

Sponsors & Collaborators

• University Hospital, Grenoble: lead
• Genoscience Pharma: collaborator

Study Sites (1)

University Hospital

Grenoble, 38043, France

Location

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

atezolizumab; 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

• Gaël ROTH, MD PHD

  University Hospital, Grenoble

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2022
• First Posted: July 7, 2022
• Study Start: December 15, 2022
• Primary Completion: March 8, 2024
• Study Completion: March 8, 2024
• Last Updated: April 20, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)