Table 3.
Summary of clinical trials evaluating therapeutic efficacy of rhArg1-PEG for cancer therapy.
| Title | Status | Conditions | Interventions | Phases | Start Date | Enrollment | Outcome | NCT | Ref |
|---|---|---|---|---|---|---|---|---|---|
| Study of PEGylated Human Recombinant Arginase for Liver Cancer | Completed | HCC | rhArg1-PEG + Doxorubicin | Phase I | 2008/5/1 | 15 | NA | NCT00988195 | |
| Study of PEGylated Human Recombinant Arginase for Liver Cancer (BCT-100-002) | Completed | HCC | rhArg1-PEG | Phase I/II | 2010/3/1 | 20 | May be included in NCT02089763. | NCT01092091 | [152] |
| A Pilot Study of Recombinant Human Arginase 1 (rhArg1) in Patients with Relapsed or Refractory Leukemia or Lymphoma | Terminated | Leukemia and Lymphoma | rhArg1-PEG | Phase I | 2012/4/1 | 1 | NA | NCT01551628 | |
| Efficacy Study of PEGylated Recombinant Human Arginase 1 as a Second-line Therapy in Patients with Advanced Liver Cancer | Completed | HCC | rhArg1-PEG | Phase II | 2014/4/1 | 27 | 27 patients were recruited, with a median TTP and PFS of 6 (95% CI, 5.9–6.0) weeks and a DCR of 21.7% (5 SD). The drug was well tolerated. Duration of arginine depletion correlated with OS. Among patients with available IHC results, those with ASS1-negative tumors had an OS of 35 (95% CI: 8.3–78.0) weeks, compared to 15.14 (95% CI: 13.4–15.1) weeks in those with ASS1-positive tumors. | NCT02089763 | [152] |
| PEGylated Recombinant Human Arginase 1 in Combination with Oxaliplatin and Capecitabine for the Treatment of HCC | Completed | HCC | rhArg1-PEG + Oxaliplatin + Capecitabine | Phase II | 2014/4/1 | 17 | 17 patients received oxaliplatin at 3 dose levels: 85 mg/m2 (8 patients), 100 mg/m2 (3 patients), and 130 mg/m2 (6 patients), with no dose-limiting toxicity. Median study duration was 8 weeks. Among 14 evaluable cases, one achieved PR, 4 had SD, and the DCR was 36%. Most responses occurred in the 130 mg/m2 cohort with 1 PR and 2 SD. Median TTP and PFS were both 7.0 weeks. Overall median OS was 10.7 months, and median OS was not reached at 19.4 months of follow-up in the 130 mg/m2 cohort. | NCT02089633 | [153] |
| Recombinant Human Arginase 1 (rhArg1) in Patients with Advanced Arginine Auxotrophic Solid Tumors | Completed | Melanoma and Prostate cancer | rhArg1-PEG | Phase I | 2014/11/1 | 23 | A 65-year-old patient with metastatic melanoma, who failed two immunotherapy strategies, received 2 mg/kg intravenously weekly BCT-100. The patient had no toxicities > grade 2 and achieved CR for over 30 months. The tumor lacked expression of ASS1 and OTC. | NCT02285101 | [155] |
| Efficacy and Safety Study of Recombinant Human Arginase 1 in Patients with Relapsed or Refractory Acute Myeloid Leukemia | Unknown | AML | rhArg1-PEG | Phase II | 2016/9/1 | Estimated 25 | NA | NCT02899286 | |
| A Study Evaluating the Safety and Activity of PEGylated Recombinant Human Arginase (BCT-100) | Completed | AML and ALL | rhArg1-PEG | Phase I/II | 2018/8/28 | 49 | NA | NCT03455140 |
Abbreviation: HCC, hepatocellular carcinoma; AML, acute myeloid leukemia; ALL, acute lymphoblastic leukemia; OS, overall survival; PFS, progression-free survival; TTP, time-to-tumor progression; SD, stable disease; DCR, disease control rate; PR, partial response; CR, complete response.