Phase I study of intravenously administered ATI-1123, a liposomal docetaxel formulation in patients with advanced solid tumors

Abstract

Purpose

ATI-1123 is a liposomal formulation of docetaxel and may be administered without the premedications and hypersensitivity reactions. This Phase I study examines the safety, tolerability, pharmacokinetics (PKs), and antitumor activity of ATI-1123.

Methods

Patients with advanced solid malignancies received escalating doses of ATI-1123 intravenously over 1-h every 3 weeks. The dosing commenced using an accelerated titration design and was followed by a modified 3 + 3 Fibonacci schema to determine maximally tolerated dose (MTD). Plasma was analyzed for encapsulated/non-encapsulated docetaxel; PK analyses were performed using model independent method. Response was assessed using RECIST criteria.

Results

In total, 29 patients received doses ranging from 15 to 110 mg/m2. At 110 mg/m2, two of six patients experienced dose-limiting toxicities including grade 3 stomatitis and febrile neutropenia. The 90 mg/m2 cohort was expanded to ten patients and identified as the MTD. The most common adverse events were fatigue, nausea, neutropenia, anemia, anorexia, and diarrhea. ATI-1123 exhibited linear and dose proportional PKs. One patient with lung cancer had confirmed partial response, and stable disease was observed in 75 % patients.

Conclusions

ATI-1123 demonstrated an acceptable tolerability and favorable PK profile in patients with solid tumors. Our results provide support for Phase II trials to determine the antitumor activity of this drug.

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Acknowledgments

The authors wish to express their deep appreciation to Ms. Susan Beardslee for reviewing the manuscript and providing very valuable comments. This study was sponsored by Azaya Therapeutics.

Conflict of interest

None to declare.

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Correspondence to Devalingam Mahalingam.

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Mahalingam, D., Nemunaitis, J.J., Malik, L. et al. Phase I study of intravenously administered ATI-1123, a liposomal docetaxel formulation in patients with advanced solid tumors. Cancer Chemother Pharmacol 74, 1241–1250 (2014). https://doi.org/10.1007/s00280-014-2602-x

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Keywords

  • ATI-1123
  • Docetaxel
  • Safety
  • Tolerability
  • Pharmacokinetics