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Updated: Nov 15, 2025
Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
Phase 1 trial of ADI-PEG20 plus cisplatin in patients with pretreated metastatic melanoma or other advanced solid
Shuyang Yao1,2, Filip Janku1, Vivek Subbiah1
1Departments of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Background:
Arginine depletion interferes with pyrimidine metabolism and DNA damage-repair pathways, and pairing arginine deiminase pegylated with 20,000-molecular-weight polyethylene glycol (ADI-PEG20) with platinum enhances cytotoxicity in vitro and in vivo in arginine auxotrophs.
Methods:
This single-centre, Phase 1 trial was conducted using a 3 + 3 dose escalation designed to assess safety, tolerability and determine the recommended Phase 2 dose (RP2D) of ADI-PEG20.
Results:
We enrolled 99 patients with metastatic argininosuccinate synthetase 1 (ASS1) deficient malignancies. We observed no dose-limiting toxic effects or treatment-related mortality. Three percent of patients discontinued treatment because of toxicity. After treatment, 5% (5/99) of patients had partial responses, and 41% had stable disease. The median progression-free and overall survival durations were 3.62 and 8.06 months, respectively. Substantial arginine depletion and citrulline escalation persisted in most patients through weeks 24 and 8, respectively. Tumour responses were associated with anti-ADI-PEG20 antibody levels at weeks 8 and 16 (p = 0.031 and p = 0.0357, respectively).
Conclusion:
Concurrently administered ADI-PEG20 and cisplatin had an acceptable safety profile and had shown antitumour activity against metastatic ASS1-deficient solid tumours. Further evaluation of this treatment combination is warranted.
Insights
Arginine deiminase pegylated (ADI-PEG20) combined with platinum chemotherapy shows safety and antitumour activity in patients with ASS1-deficient cancers. This combination warrants further investigation for treating metastatic solid tumours.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Arginine depletion impacts pyrimidine metabolism and DNA repair.
- Pegylated arginine deiminase (ADI-PEG20) combined with platinum enhances cytotoxicity in arginine auxotrophs.
Purpose of the Study:
- Assess the safety and tolerability of ADI-PEG20.
- Determine the recommended Phase 2 dose (RP2D) of ADI-PEG20 in patients with ASS1-deficient malignancies.
Main Methods:
- Single-centre, Phase 1 dose escalation trial.
- 99 patients with metastatic argininosuccinate synthetase 1 (ASS1) deficient malignancies enrolled.
- 3+3 design used to assess safety and tolerability.
Main Results:
- No dose-limiting toxicities or treatment-related mortality observed.
- 5% partial responses and 41% stable disease achieved.
- Median progression-free survival: 3.62 months; overall survival: 8.06 months.
Conclusions:
- ADI-PEG20 and cisplatin demonstrate an acceptable safety profile.
- The combination exhibits antitumour activity in metastatic ASS1-deficient solid tumours.
- Further evaluation of this combination is recommended.
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