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Clinical Trial
. 2014 Jul 1;20(13):3581-8.
doi: 10.1158/1078-0432.CCR-13-2686. Epub 2014 Apr 11.

A phase I trial of LY2510924, a CXCR4 peptide antagonist, in patients with advanced cancer

Matthew D Galsky  1 , Nicholas J Vogelzang  2 , Paul Conkling  3 , Eyas Raddad  4 , John Polzer  4 , Stephanie Roberson  4 , John R Stille  4 , Mansoor Saleh  5 , Donald Thornton  6
Affiliations
Clinical Trial

A phase I trial of LY2510924, a CXCR4 peptide antagonist, in patients with advanced cancer

Matthew D Galsky et al. Clin Cancer Res. .

Erratum in

  • Clin Cancer Res. 2014 Aug 15;20(16):4414

Abstract

Purpose: Overexpression of C-X-C motif receptor 4 (CXCR4) is implicated in tumor progression. LY2510924 is a peptide antagonist, which blocks stromal cell-derived factor-1 (SDF1) from CXCR4 binding.

Experimental design: This phase I study included two parts: a 3+3 dose escalation (part A) and dose confirmation (part B). LY2510924 was administered as a daily subcutaneous injection on a 28-day cycle. The primary objective was to determine the recommended phase II dose. Secondary objectives included safety, pharmacokinetics, efficacy, and pharmacodynamic response, including mobilization of CD34(+) hematopoietic stem cells into the peripheral blood.

Results: Forty-five patients were enrolled, 25 in part A and 20 in part B. Patients were administered increasing doses of LY2510924: 1.0, 2.5, 5.0, 10, 20, and 30 mg/day for part A and 2.5 or 20 mg/day for part B. Two patients (30-mg/day cohort) experienced dose-limiting toxicities of grade 3 increased neutrophil count. The maximum tolerated dose (MTD) was 20 mg/day. The most common drug-related treatment-emergent adverse events were fatigue (9%), injection-site reaction (9%), injection site pruritus (7%), and nausea (7%). The best response was stable disease for nine patients (20%). At the end of cycle 1, mean peak LY2510924 plasma concentration and the 24-hour area under the plasma concentration versus time curve increased slightly more than dose proportionally. LY2510924 dose dependently increased CD34(+) cell counts in peripheral blood up to 18-fold.

Conclusions: LY2510924 demonstrated CD34(+) cell mobilization at doses ≥2.5 mg/day with a tolerable safety profile up to an MTD of 20 mg/day.

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