Study of ADI-PEG 20 Versus Placebo in Subjects With High Arginine Level and Unresectable Hepatocellular Carcinoma

NCT05317819 | Recruiting Phase 3 DMC

• 1 other identifier: POLARIS2021-001
• Study Type: interventional
• Target: 300
• Locations: 2 countries
• Sites: 11

Brief Summary

Evaluate efficacy and safety of ADI-PEG 20 in patients with high-argininephenotypic and HCC

Conditions

Hepatocellular Carcinoma; Advanced Hepatocellular Carcinoma

Keywords

Unresectable Hepatocellular Carcinoma; Genotype; Arginine; Arginine Deiminase; ADI-PEG 20; pegargiminase

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Time from study enrollment to death

  Approximately 18 months

Secondary Outcomes (1)

• Progression free survival

  Approximately 18 months

Study Arms (2)

Drug: ADI-PEG 20

EXPERIMENTAL

Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM)

Drug: ADI-PEG20

Drug: Placebo

PLACEBO COMPARATOR

Dose: 36 mg/m2 given weekly Route of Administration: Intramuscular (IM)

Other: Placebo

Interventions

ADI-PEG20 DRUG

Treatment for hepatocellular carcinoma

Also known as: pegargiminase

Drug: ADI-PEG 20

Placebo OTHER

Treatment for hepatocellular carcinoma

Drug: Placebo

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior diagnosis of HCC confirmed by radiology, histology, or cytology.
• Prior treatment with at least 1 systemic agent for Child-Pugh A subjects. However, Child-Pugh B7 subjects without prior systemic treatment may be enrolled, if they are not eligible for any approved systemic therapies (e.g., due to financial factors).
• Plasma arginine ≥ 78 μM at pre-screening visit.
• Measurable disease using RECIST 1.1 (Appendix A). At least 1 measurable lesion must be present. Subjects who have received local-regional therapies are eligible, provided that they have either a target lesion which has not been treated with local therapy and/or the target lesion(s) within the field of the local regional therapy has shown an increase of ≥ 20% in size. Local-regional therapy must be completed at least 4 weeks prior to the baseline CT scan.
• Child-Pugh (cirrhosis status) score class A-B7 (Appendix C).
• Barcelona Cancer of the Liver (BCLC) stage C (Appendix B)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 at enrollment (Appendix D).
• Expected survival of at least 3 months.
• Age \>18 years.
• Fully recovered from prior surgery, radiation, or chemotherapy, and none within 2 weeks prior to week 1 visit. Liver biopsy for HCC confirmation is allowed.
• Female subjects and male subjects must be asked to use appropriate contraception for both the male and female for the duration of the study and for 35 days after last dose of ADI-PEG 20/placebo. Male partners of female subjects and female partners of male subjects must agree to use two forms of contraception or agree to refrain from intercourse for the duration of the study if they are of childbearing potential. Females of childbearing potential must not be pregnant at the start of the study, and a serum human chorionic gonadotropin (HCG) pregnancy test must be negative before entry into the study. If positive HCG pregnancy test, further evaluation to rule out pregnancy must be performed according to GCP before this subject is deemed eligible. Females not of childbearing potential must be post-menopausal (defined as cessation of regular menstrual period for at least 12 months).
• Informed consent must be obtained prior to study initiation.
• No concurrent investigational studies are allowed.
• Total bilirubin \< 3.0 mg/dL and no evidence of bile obstruction.
• Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤5 x upper limit of normal range.

You may not qualify if:

• Candidate for potential curative therapies (i.e., resection or transplantation) or eligible for approved systemic therapies according to the labeling of such drugs.
• Prior allograft transplantation including liver transplantation.
• Subjects who have not fully recovered from toxicities associated with previous HCC loco-regional or systemic therapies, except for Grade 1 alopecia.
• Serious infection requiring treatment with intravenous, systemically administered antibiotics at the time of study entrance, or an infection requiring systemic antibiotic therapy within 7 days prior to the first dose of study treatment.
• Pregnancy or lactation.
• Expected non-compliance.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), cardiac arrhythmia, or psychiatric illness, social situations that would limit compliance with study requirements.
• Subjects with history of another primary cancer, including co-existent second malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b) curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no known active disease present or in the opinion of the investigator will not affect patient outcome.
• Subjects who had been treated with ADI-PEG 20 previously.
• History of uncontrolled seizure disorder not related to underlying cancer.
• Allergy to pegylated compounds.
• Allergy to E. coli drug products (such as GMCSF).
• Bleeding esophageal or gastric varices within the prior three months, except if banded or treated.
• Uncontrolled ascites (defined as not easily controlled with diuretic treatment).
• Having received any blood transfusion, blood component preparation, erythropoietin, albumin preparation, or granulocyte colony stimulating factors (G-CSF) within 7 days prior to screening laboratories or after screening laboratories have been obtained until week 1 visit.

Sponsors & Collaborators

• Polaris Group: lead

Study Sites (11)

Changhua Christian Hospital (CCH)

Changhua, 500, Taiwan

RECRUITING

Ditmanson Medical Foundation Chiayi Christian Hospital (CYCH)

Chiayi City, 600, Taiwan

RECRUITING

Chang Gung Medical Foundation-Chia-Yi (CGMF-CY)

Chiayi City, 613, Taiwan

RECRUITING

Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUH)

Kaohsiung City, 807, Taiwan

RECRUITING

Chang Gung Medical Foundation-Kaohsiung(CGMF-KS)

Kaohsiung City, 833, Taiwan

RECRUITING

Chi Mei Medical Center (CMMC-YK)

Tainan, 710, Taiwan

RECRUITING

Chi Mei Hospital, Liouying (CMMC-LY)

Tainan, 736, Taiwan

RECRUITING

Chang Gung Medical Foundation-Linkou (CGMF-LK)

Taoyuan District, 333, Taiwan

RECRUITING

Bach Mai Hospital

Hanoi, 100000, Vietnam

NOT YET RECRUITING

K Hospital

Hà Nội, 100000, Vietnam

NOT YET RECRUITING

Hue Central Hospital

Huế, 49000, Vietnam

NOT YET RECRUITING

MeSH Terms

Conditions

Carcinoma, Hepatocellular

Interventions

ADI PEG20

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

Study Officials

• John S Bomalaski

  Polaris Group

  STUDY DIRECTOR

Central Study Contacts

Maureen Liu

CONTACT

+886226562727; mliu@polarispharma.com

Doris Cheng

CONTACT

+886226562727; dorischeng@polarispharma.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: This is a randomized, double-blind trial.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: To evaluate efficacy and safety of ADI-PEG 20 or Placebo in patients with high-arginine-phenotypic and HCC

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: April 8, 2022
• Study Start: March 14, 2022
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: December 18, 2025

Record last verified: 2025-11

Locations

TW (8); VN (3)