A multicenter phase 1 study of PX-866 in combination with docetaxel in patients with advanced solid tumours

D. W. Bowles, W. W. Ma, N. Senzer, J. R. Brahmer, A. A. Adjei, M. Davies, A. J. Lazar, A. Vo, S. Peterson, L. Walker, D. Hausman, C. M. Rudin, A. Jimeno

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46 Scopus citations

Abstract

Background:This phase I, dose-finding study determined the safety, maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D), pharmacokinetics, and antitumour activity of PX-866, a phosphatidylinositol 3-kinase inhibitor, combined with docetaxel in patients with incurable solid tumours.Methods:PX-866 was administered at escalating doses (4-8 mg daily) with docetaxel 75 mg m -2 intravenously every 21 days. Archived tumour tissue was assessed for potential predictive biomarkers.Results:Forty-three patients were enrolled. Most adverse events (AEs) were grade 1 or 2. The most frequent study drug-related AE was diarrhoea (76.7%), with gastrointestinal disorders occurring in 79.1% (docetaxel-related) and 83.7% (PX-866-related). No dose-limiting toxicities were observed. The RP2D was 8 mg, the same as the single-agent MTD. Co-administration of PX-866 and docetaxel did not affect either drug's PKs. Best responses in 35 evaluable patients were: 2 partial responses (6%), 22 stable disease (63%), and 11 disease progression (31%). Eleven patients remained on study for >180 days, including 8 who maintained disease control on single-agent PX-866. Overall median progression-free survival (PFS) was 73.5 days (range: 1-569). A non-significant association between longer PFS for PIK3CA-MUT/KRAS-WT vs PIK3CA-WT/KRAS-WT was observed.Conclusion:Treatment with PX-866 and docetaxel was well tolerated, without evidence of overlapping/cumulative toxicity. Further investigation with this combination is justified.

Original languageEnglish (US)
Pages (from-to)1085-1092
Number of pages8
JournalBritish journal of cancer
Volume109
Issue number5
DOIs
StatePublished - Sep 2013

Keywords

  • PIK3CA; PI3K; phase 1; docetaxel; combination therapy

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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