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A phase 1 study of ADI-PEG 20 and modified FOLFOX6 in patients with advanced hepatocellular carcinoma and other

James J Harding1,2,3, Richard K Do4,5, Imane El Dika4

  • 1Memorial Sloan Kettering Cancer Center, New York, NY, USA. Hardinj1@mskcc.org.

Cancer Chemotherapy and Pharmacology
|July 5, 2018
PubMed
Abstract

Insights

This Phase 1 trial found that combining pegylated arginine deiminase (ADI-PEG 20) with modified FOLFOX6 (mFOLFOX6) is safe and effective for advanced hepatocellular carcinoma (HCC). The recommended dose of ADI-PEG 20 is 36 mg/m² weekly.

Area of Science:

  • Oncology
  • Pharmacology
  • Gastroenterology

Background:

  • Arginine depletion disrupts pyrimidine metabolism and DNA repair.
  • Preclinical studies suggest pegylated arginine deiminase (ADI-PEG 20) combined with chemotherapy enhances cancer cell death.

Purpose of the Study:

  • To assess the safety, tolerability, and recommended Phase 2 dose (RP2D) of ADI-PEG 20 combined with modified FOLFOX6 (mFOLFOX6).
  • To determine the objective response rate (ORR) in patients with advanced hepatocellular carcinoma (HCC).

Main Methods:

  • A single-center, open-label, Phase 1 dose-escalation trial using a 3+3 design.
  • Patients received mFOLFOX6 biweekly and ADI-PEG 20 weekly at escalating doses (18 or 36 mg/m²).
  • An expansion cohort at the RP2D (36 mg/m²) was used to evaluate ORR, progression-free survival (PFS), and overall survival (OS).

Main Results:

  • The RP2D of ADI-PEG 20 was determined to be 36 mg/m² weekly with mFOLFOX6.
  • The ORR in 23 HCC patients was 21% (95% CI 7.5-43.7), with median PFS of 7.3 months and median OS of 14.5 months.
  • Common adverse events included thrombocytopenia and neutropenia; no dose-limiting toxicities were observed.

Conclusions:

  • Concurrent mFOLFOX6 and ADI-PEG 20 (36 mg/m² weekly) demonstrate an acceptable safety profile and promising efficacy in advanced HCC.
  • This combination warrants further investigation in advanced HCC patients.
Keywords:
ADI-PEG 20ArginineArginine deiminaseArgininosuccinate synthetase-1FOLFOXHepatocellular carcinoma

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