A phase 1 study of pegylated recombinant arginase (PEG-BCT-100) in combination with systemic chemotherapy (capecitabine and oxaliplatin)[PACOX] in advanced hepatocellular carcinoma patients

Invest New Drugs. 2022 Apr;40(2):314-321. doi: 10.1007/s10637-021-01178-3. Epub 2021 Nov 4.

Abstract

Introduction: We investigated the safety and efficacy of a pegylated arginase (PEG-BCT-100) in combination with chemotherapy (oxaliplatin and capecitabine) [PACOX] in advanced HCC patients.

Methods: This was a single centre phase 1 trial to assess the safety and tolerability of PACOX. All the enrolled subjects received treatment in 3-weekly cycles: intravenous PEG-BCT-100 2.7 mg/kg on days 1, 8 and 15 of each cycle; oral capecitabine 1000 mg/m2 twice daily on day 1-14 of each cycle and intravenous oxaliplatin on day 1. Three dose levels of oxaliplatin (85 mg/m2, 100 mg/m2 or 130 mg/m2) were studied to define the maximum tolerated dose (MTD). Adverse events (AEs), efficacy by RECIST v1.1, time to progression (TTP), progression-free survival (PFS) and overall survival (OS) were studied.

Results: Seventeen patients were enrolled at 3 dose levels of oxaliplatin: 85 mg/m2 (8 patients), 100 mg/m2 (3 patients), and 130 mg/m2 (6 patients). The median age was 55 years; all had had locoregional chemotherapy or targeted therapy such as sorafenib, but no systemic chemotherapy. The most common AEs were nausea (82%), injection site reaction (76%), palmar-plantar erythrodysesthesia (59%), oral mucositis (53%) and vomiting (53%). There was no dose-limiting toxicity (DLT). Median duration on study was 8 weeks overall. In 14 evaluable cases, one achieved partial response (PR), 4 had stable disease (SD); disease control rate was 36%; most responses were observed in the 130 mg/m2 cohort with 1 PR and 2 SDs. Median TTP and PFS were both 7.0 weeks. Overall median OS was 10.7 months; the median OS was not reached at 19.4 months of follow-up in the 130 mg/m2 cohort.

Conclusion: The PACOX regimen demonstrated good anti-cancer activity and survival advantage in advanced pre-treated HCC with favourable safety profile. It warrants further phase II/III studies.

Keywords: Arginine; Capecitabine; Hepatocellular carcinoma; Oxaliplatin; PEG-BCT-100.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Arginase
  • Capecitabine
  • Carcinoma, Hepatocellular* / drug therapy
  • Fluorouracil / adverse effects
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / pathology
  • Middle Aged
  • Oxaliplatin
  • Polyethylene Glycols / adverse effects
  • Recombinant Proteins

Substances

  • BCT-100
  • Recombinant Proteins
  • Oxaliplatin
  • Polyethylene Glycols
  • Capecitabine
  • Arginase
  • Fluorouracil